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1.
Arterioscler Thromb Vasc Biol ; 39(9): 1859-1873, 2019 09.
Article in English | MEDLINE | ID: mdl-31315432

ABSTRACT

OBJECTIVE: Marfan syndrome (MFS) is caused by mutations in FBN1 (fibrillin-1), an extracellular matrix (ECM) component, which is modified post-translationally by glycosylation. This study aimed to characterize the glycoproteome of the aortic ECM from patients with MFS and relate it to aortopathy. Approach and Results: ECM extracts of aneurysmal ascending aortic tissue from patients with and without MFS were enriched for glycopeptides. Direct N-glycopeptide analysis by mass spectrometry identified 141 glycoforms from 47 glycosites within 35 glycoproteins in the human aortic ECM. Notably, MFAP4 (microfibril-associated glycoprotein 4) showed increased and more diverse N-glycosylation in patients with MFS compared with control patients. MFAP4 mRNA levels were markedly higher in MFS aortic tissue. MFAP4 protein levels were also increased at the predilection (convexity) site for ascending aorta aneurysm in bicuspid aortic valve patients, preceding aortic dilatation. In human aortic smooth muscle cells, MFAP4 mRNA expression was induced by TGF (transforming growth factor)-ß1 whereas siRNA knockdown of MFAP4 decreased FBN1 but increased elastin expression. These ECM changes were accompanied by differential gene expression and protein abundance of proteases from ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) family and their proteoglycan substrates, respectively. Finally, high plasma MFAP4 concentrations in patients with MFS were associated with a lower thoracic descending aorta distensibility and greater incidence of type B aortic dissection during 68 months follow-up. CONCLUSIONS: Our glycoproteomics analysis revealed that MFAP4 glycosylation is enhanced, as well as its expression during the advanced, aneurysmal stages of MFS compared with control aneurysms from patients without MFS.


Subject(s)
Aorta/chemistry , Extracellular Matrix/chemistry , Glycopeptides/analysis , Marfan Syndrome/metabolism , Proteomics/methods , Aortic Aneurysm, Thoracic/metabolism , Carrier Proteins/blood , Carrier Proteins/genetics , Carrier Proteins/physiology , Extracellular Matrix Proteins/blood , Extracellular Matrix Proteins/genetics , Extracellular Matrix Proteins/physiology , Fibrillin-1/genetics , Glycoproteins/blood , Glycoproteins/genetics , Glycoproteins/physiology , Glycosylation , Humans , Myocytes, Smooth Muscle/metabolism , Vascular Remodeling
2.
Thorac Cardiovasc Surg ; 68(4): 352-356, 2020 06.
Article in English | MEDLINE | ID: mdl-30736084

ABSTRACT

OBJECTIVES: Patients undergoing surgery for locally advanced lung cancer involving the chest wall require anatomical lung with extensive en-bloc chest wall resection and appropriate reconstruction.In this proof-of-concept study, we aimed to produce personalized three-dimensional (3D)-printed chest wall prosthesis for a patient undergoing chest wall resection and reconstruction using clinically obtained computed tomography (CT) data. METHODS: Preoperative CT scans of three patients undergoing chest wall resection were analyzed and the areas of resection segmented. This was then used to produce a 3D print of the chest wall and a silicone mold was created from the model. This mold was sterilized and used to produce methyl methacrylate prostheses which were then implanted into the patients. RESULTS: Three patients had their chest wall reconstructed using this technique to produce a patient specific prosthesis. There were no early complications or deaths. CONCLUSIONS: It is possible to use 3D printing to produce a patient specific chest wall reconstruction for patients undergoing chest wall resection for malignancy that is cost-effective. This chest wall is thought to provide stability in the form of prosthetic ribs as well compliance in the form of an expanded polytetrafluoroethylene patch. Further research is required to measure chest wall compliance during the respiratory cycle and long-term follow-up from this method.


Subject(s)
Breast Neoplasms/surgery , Lung Neoplasms/surgery , Methylmethacrylate , Plastic Surgery Procedures/instrumentation , Printing, Three-Dimensional , Prosthesis Design , Thoracic Surgical Procedures/instrumentation , Thoracic Wall/surgery , Aged , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/pathology , Female , Humans , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/pathology , Male , Middle Aged , Neoplasm Invasiveness , Patient-Specific Modeling , Proof of Concept Study , Plastic Surgery Procedures/adverse effects , Thoracic Surgical Procedures/adverse effects , Thoracic Wall/diagnostic imaging , Thoracic Wall/pathology , Tomography, X-Ray Computed , Treatment Outcome
3.
Circulation ; 137(2): 166-183, 2018 01 09.
Article in English | MEDLINE | ID: mdl-29030347

ABSTRACT

BACKGROUND: Extracellular matrix (ECM) remodeling contributes to in-stent restenosis and thrombosis. Despite its important clinical implications, little is known about ECM changes post-stent implantation. METHODS: Bare-metal and drug-eluting stents were implanted in pig coronary arteries with an overstretch under optical coherence tomography guidance. Stented segments were harvested 1, 3, 7, 14, and 28 days post-stenting for proteomics analysis of the media and neointima. RESULTS: A total of 151 ECM and ECM-associated proteins were identified by mass spectrometry. After stent implantation, proteins involved in regulating calcification were upregulated in the neointima of drug-eluting stents. The earliest changes in the media were proteins involved in inflammation and thrombosis, followed by changes in regulatory ECM proteins. By day 28, basement membrane proteins were reduced in drug-eluting stents in comparison with bare-metal stents. In contrast, the large aggregating proteoglycan aggrecan was increased. Aggrecanases of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) family contribute to the catabolism of vascular proteoglycans. An increase in ADAMTS-specific aggrecan fragments was accompanied by a notable shift from ADAMTS1 and ADAMTS5 to ADAMTS4 gene expression after stent implantation. Immunostaining in human stented coronary arteries confirmed the presence of aggrecan and aggrecan fragments, in particular, at the contacts of the stent struts with the artery. Further investigation of aggrecan presence in the human vasculature revealed that aggrecan and aggrecan cleavage were more abundant in human arteries than in human veins. In addition, aggrecan synthesis was induced on grafting a vein into the arterial circulation, suggesting an important role for aggrecan in vascular plasticity. Finally, lack of ADAMTS-5 activity in mice resulted in an accumulation of aggrecan and a dilation of the thoracic aorta, confirming that aggrecanase activity regulates aggrecan abundance in the arterial wall and contributes to vascular remodeling. CONCLUSIONS: Significant differences were identified by proteomics in the ECM of coronary arteries after bare-metal and drug-eluting stent implantation, most notably an upregulation of aggrecan, a major ECM component of cartilaginous tissues that confers resistance to compression. The accumulation of aggrecan coincided with a shift in ADAMTS gene expression. This study provides the first evidence implicating aggrecan and aggrecanases in the vascular injury response after stenting.


Subject(s)
ADAMTS Proteins/metabolism , Aggrecans , Coronary Vessels/surgery , Endopeptidases/metabolism , Extracellular Matrix/enzymology , Percutaneous Coronary Intervention/instrumentation , Proteomics/methods , Stents , Vascular Remodeling , ADAMTS Proteins/genetics , ADAMTS5 Protein/genetics , ADAMTS5 Protein/metabolism , Animals , Chromatography, High Pressure Liquid , Coronary Vessels/enzymology , Coronary Vessels/physiopathology , Drug-Eluting Stents , Endopeptidases/genetics , Female , Humans , Male , Metals , Mice, Knockout , Models, Animal , Neointima , Prosthesis Design , Signal Transduction , Sus scrofa , Tandem Mass Spectrometry , Time Factors
4.
Arterioscler Thromb Vasc Biol ; 38(7): 1537-1548, 2018 07.
Article in English | MEDLINE | ID: mdl-29622560

ABSTRACT

OBJECTIVE: Thoracic aortic aneurysm (TAA), a degenerative disease of the aortic wall, is accompanied by changes in the structure and composition of the aortic ECM (extracellular matrix). The ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) family of proteases has recently been implicated in TAA formation. This study aimed to investigate the contribution of ADAMTS-5 to TAA development. APPROACH AND RESULTS: A model of aortic dilatation by AngII (angiotensin II) infusion was adopted in mice lacking the catalytic domain of ADAMTS-5 (Adamts5Δcat). Adamts5Δcat mice showed an attenuated rise in blood pressure while displaying increased dilatation of the ascending aorta (AsAo). Interestingly, a proteomic comparison of the aortic ECM from AngII-treated wild-type and Adamts5Δcat mice revealed versican as the most upregulated ECM protein in Adamts5Δcat mice. This was accompanied by a marked reduction of ADAMTS-specific versican cleavage products (versikine) and a decrease of LRP1 (low-density lipoprotein-related protein 1). Silencing LRP1 expression in human aortic smooth muscle cells reduced the expression of ADAMTS5, attenuated the generation of versikine, but increased soluble ADAMTS-1. A similar increase in ADAMTS-1 was observed in aortas of AngII-treated Adamts5Δcat mice but was not sufficient to maintain versican processing and prevent aortic dilatation. CONCLUSIONS: Our results support the emerging role of ADAMTS proteases in TAA. ADAMTS-5 rather than ADAMTS-1 is the key protease for versican regulation in murine aortas. Further studies are needed to define the ECM substrates of the different ADAMTS proteases and their contribution to TAA formation.


Subject(s)
ADAMTS5 Protein/metabolism , Aorta, Thoracic/enzymology , Aortic Aneurysm, Thoracic/enzymology , Extracellular Matrix/enzymology , Vascular Remodeling , ADAMTS1 Protein/metabolism , ADAMTS5 Protein/deficiency , ADAMTS5 Protein/genetics , Angiotensin II , Animals , Aorta, Thoracic/pathology , Aortic Aneurysm, Thoracic/chemically induced , Aortic Aneurysm, Thoracic/genetics , Aortic Aneurysm, Thoracic/pathology , Cells, Cultured , Dilatation, Pathologic , Disease Models, Animal , Extracellular Matrix/pathology , Humans , Low Density Lipoprotein Receptor-Related Protein-1/genetics , Low Density Lipoprotein Receptor-Related Protein-1/metabolism , Male , Mice, Knockout , Muscle, Smooth, Vascular/enzymology , Myocytes, Smooth Muscle , Receptors, LDL/metabolism , Tumor Suppressor Proteins/metabolism , Versicans/metabolism
5.
Int J Behav Med ; 26(3): 316-322, 2019 Jun.
Article in English | MEDLINE | ID: mdl-30793258

ABSTRACT

BACKGROUND: The relationship between pre-surgical distress and diurnal cortisol following surgery has not been investigated prospectively in caregivers of coronary artery bypass graft (CABG) patients before. We aimed to examine the relationship between pre-surgical anxiety and caregiver burden and diurnal cortisol measured 2 months after the surgery in the caregivers of CABG patients. METHOD: We used a sample of 103 caregivers of elective CABG patients that were assessed 28.86 days before and 60.94 days after patients' surgery. Anxiety and caregiver burden were assessed using the anxiety subscale of the Hospital Anxiety and Depression Scale and the Oberst Burden Scale respectively. Saliva samples were collected to measure cortisol area under the curve with respect to ground (AUCg) and diurnal cortisol slope. Anxiety and caregiver burden were entered into linear regression models simultaneously. RESULTS: While high levels of pre-surgical anxiety were positively associated with increased follow-up levels of AUCg (ß = 0.30, p = 0.001), greater pre-surgery perceived burden score was associated with steeper cortisol slope (ß = 0.27, p = 0.017) after controlling for a wide range of covariates. CONCLUSION: These outcomes support the utility of psychological interventions aimed to increase the awareness of caregiving tasks and demands in informal caregivers.


Subject(s)
Anxiety/psychology , Caregivers/psychology , Coronary Artery Bypass/psychology , Hydrocortisone/analysis , Adaptation, Psychological , Aged , Depression/psychology , Female , Humans , Male , Middle Aged , Perception , Saliva/chemistry
6.
Europace ; 20(7): 1201-1208, 2018 07 01.
Article in English | MEDLINE | ID: mdl-28582578

ABSTRACT

Aims: Post-operative atrial fibrillation (POAF) is a predictor of morbidity and mortality after cardiac surgery. Latent predisposing factors may reside in the epicardial adipose tissue (EAT) due to its anatomical position and high protein production rate. In order to explore a possible mechanistic link, we characterized proteins secreted by the EAT preceding the onset of POAF. Methods and results: Epicardial adipose tissue samples were collected from 76 consecutive patients with no history of AF undergoing coronary artery bypass surgery, 50 samples for proteomic analysis and 26 for gene expression studies, further divided according to development of POAF. Ten vs. 10 matched samples representing EAT secretome were analysed by two-dimensional difference in-gel electrophoresis (2D-DIGE) and high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) to identify differentially expressed proteins (P < 0.05, expression change >1.2 fold). Findings were validated by Western blotting on EAT protein extracts and by gene expression studies via quantitative polymerase chain reaction (qPCR). Proteomics returned 35 differentially expressed proteins. Amongst those, gelsolin was down regulated in POAF. Western blot analysis confirmed a significant reduction in gelsolin in the AF group. Gene expression for gelsolin was significantly reduced in the AF group confirming the proteomics findings. Conclusion: For the first time we describe EAT secretome as a possible substrate for POAF. It contains various proteins differentially expressed in patients who later develop POAF. Amongst those gelsolin, involved in inflammation and ion channel regulation, was associated with maintenance of sinus rhythm. Understanding the role of EAT may offer novel insights into prevention and treatment of AF.


Subject(s)
Adipose Tissue/metabolism , Atrial Fibrillation/etiology , Coronary Artery Bypass/adverse effects , Pericardium/metabolism , Proteomics/methods , Aged , Atrial Fibrillation/diagnosis , Atrial Fibrillation/genetics , Atrial Fibrillation/metabolism , Biomarkers/metabolism , Blotting, Western , Chromatography, High Pressure Liquid , Electrophoresis, Gel, Two-Dimensional , Female , Gelsolin/genetics , Gelsolin/metabolism , Gene Expression Regulation , Humans , Male , Middle Aged , Reverse Transcriptase Polymerase Chain Reaction , Risk Factors , Secretory Pathway , Tandem Mass Spectrometry , Treatment Outcome
7.
J Biomech Eng ; 140(1)2018 Jan 01.
Article in English | MEDLINE | ID: mdl-28890987

ABSTRACT

Computational fluid dynamics (CFD) provides a noninvasive method to functionally assess aortic hemodynamics. The thoracic aorta has an anatomically complex inlet comprising of the aortic valve and root, which is highly prone to different morphologies and pathologies. We investigated the effect of using patient-specific (PS) inflow velocity profiles compared to idealized profiles based on the patient's flow waveform. A healthy 31 yo with a normally functioning tricuspid aortic valve (subject A), and a 52 yo with a bicuspid aortic valve (BAV), aortic valvular stenosis, and dilated ascending aorta (subject B) were studied. Subjects underwent MR angiography to image and reconstruct three-dimensional (3D) geometric models of the thoracic aorta. Flow-magnetic resonance imaging (MRI) was acquired above the aortic valve and used to extract the patient-specific velocity profiles. Subject B's eccentric asymmetrical inflow profile led to highly complex velocity patterns, which were not replicated by the idealized velocity profiles. Despite having identical flow rates, the idealized inflow profiles displayed significantly different peak and radial velocities. Subject A's results showed some similarity between PS and parabolic inflow profiles; however, other parameters such as Flowasymmetry were significantly different. Idealized inflow velocity profiles significantly alter velocity patterns and produce inaccurate hemodynamic assessments in the thoracic aorta. The complex structure of the aortic valve and its predisposition to pathological change means the inflow into the thoracic aorta can be highly variable. CFD analysis of the thoracic aorta needs to utilize fully PS inflow boundary conditions in order to produce truly meaningful results.


Subject(s)
Aorta, Thoracic/physiology , Hemodynamics , Patient-Specific Modeling , Aorta, Thoracic/diagnostic imaging , Humans , Imaging, Three-Dimensional , Magnetic Resonance Imaging
8.
Circulation ; 134(11): 817-32, 2016 Sep 13.
Article in English | MEDLINE | ID: mdl-27559042

ABSTRACT

BACKGROUND: Myocardial fibrosis is a feature of many cardiac diseases. We used proteomics to profile glycoproteins in the human cardiac extracellular matrix (ECM). METHODS: Atrial specimens were analyzed by mass spectrometry after extraction of ECM proteins and enrichment for glycoproteins or glycopeptides. RESULTS: ECM-related glycoproteins were identified in left and right atrial appendages from the same patients. Several known glycosylation sites were confirmed. In addition, putative and novel glycosylation sites were detected. On enrichment for glycoproteins, peptides of the small leucine-rich proteoglycan decorin were identified consistently in the flowthrough. Of all ECM proteins identified, decorin was found to be the most fragmented. Within its protein core, 18 different cleavage sites were identified. In contrast, less cleavage was observed for biglycan, the most closely related proteoglycan. Decorin processing differed between human ventricles and atria and was altered in disease. The C-terminus of decorin, important for the interaction with connective tissue growth factor, was detected predominantly in ventricles in comparison with atria. In contrast, atrial appendages from patients in persistent atrial fibrillation had greater levels of full-length decorin but also harbored a cleavage site that was not found in atrial appendages from patients in sinus rhythm. This cleavage site preceded the N-terminal domain of decorin that controls muscle growth by altering the binding capacity for myostatin. Myostatin expression was decreased in atrial appendages of patients with persistent atrial fibrillation and hearts of decorin null mice. A synthetic peptide corresponding to this decorin region dose-dependently inhibited the response to myostatin in cardiomyocytes and in perfused mouse hearts. CONCLUSIONS: This proteomics study is the first to analyze the human cardiac ECM. Novel processed forms of decorin protein core, uncovered in human atrial appendages, can regulate the local bioavailability of antihypertrophic and profibrotic growth factors.


Subject(s)
Atrial Fibrillation/metabolism , Decorin , Myostatin/antagonists & inhibitors , Peptides , Animals , Atrial Fibrillation/drug therapy , Atrial Fibrillation/pathology , Atrial Fibrillation/physiopathology , Decorin/chemistry , Decorin/metabolism , Decorin/pharmacology , Female , HEK293 Cells , Heart Atria/metabolism , Heart Atria/physiopathology , Heart Ventricles/metabolism , Heart Ventricles/physiopathology , Humans , Male , Mice , Mice, Mutant Strains , Myocytes, Cardiac/metabolism , Myocytes, Cardiac/pathology , Myostatin/metabolism , Peptides/chemical synthesis , Peptides/chemistry , Peptides/metabolism , Peptides/pharmacology , Proteomics
9.
Br Med Bull ; 121(1): 61-71, 2017 01 01.
Article in English | MEDLINE | ID: mdl-27989994

ABSTRACT

Introduction: Treatment guidelines for the thoracic aorta concentrate on size, yet acute aortic dissection or rupture can occur when aortic size is below intervention criteria. Functional imaging and computational techniques are a means of assessing haemodynamic parameters involved in aortic pathology. Sources of data: Original articles, reviews, international guidelines. Areas of agreement: Computational fluid dynamics and 4D flow MRI allow non-invasive assessment of blood flow parameters and aortic wall biomechanics. Areas of controversy: Aortic valve morphology (particularly bicuspid aortic valve) is associated with aneurysm of the ascending aorta, although the exact mechanism of aneurysm formation is not yet established. Growing points: Haemodynamic assessment of the thoracic aorta has highlighted parameters which are linked with both clinical outcome and protein changes in the aortic wall. Wall shear stress, flow displacement and helicity are elevated in patients with bicuspid aortic valve, particularly at locations of aneurysm formation. Areas timely for developing research: With further validation, functional assessment of the aorta may help identify patients at risk of aortic complications, and introduce new haemodynamic indices into management guidelines.


Subject(s)
Aortic Aneurysm, Thoracic/diagnostic imaging , Aortic Valve/abnormalities , Cardiac Imaging Techniques , Heart Valve Diseases/diagnostic imaging , Image Interpretation, Computer-Assisted/methods , Aortic Aneurysm, Thoracic/physiopathology , Aortic Valve/diagnostic imaging , Aortic Valve/pathology , Bicuspid Aortic Valve Disease , Blood Flow Velocity , Heart Valve Diseases/pathology , Hemodynamics/physiology , Humans , Magnetic Resonance Imaging , Practice Guidelines as Topic , Predictive Value of Tests
10.
Europace ; 19(9): 1521-1526, 2017 Sep 01.
Article in English | MEDLINE | ID: mdl-28340095

ABSTRACT

AIMS: Non-laser-based methods are safe in lead extraction but in the past have been less effective than laser methods. In the past decade, new equipment has been introduced including the Evolution® Mechanical Dilator Sheath and the Evolution® RL. We sought to determine the impact of new equipment on outcome in mechanical lead extraction. METHODS AND RESULTS: We considered 288 consecutive patients (age 66 ± 18 years) who underwent transvenous lead extraction (TLE) of 522 leads in the decade to the end of 2014. Three groups were identified: Group 1 (pre-Evolution® period, 76 patients, 133 leads), Group 2 (original Evolution® period, 115 patients, 221 leads), and Group 3 (Evolution® RL period, 97 patients, 168 leads). The age of leads was significantly greater in Groups 2 and 3 (6.2 ± 4.4 and 6.1 ± 5.4 years vs.4.7 ± 4.5, P < 0.05) as was the proportion of implantable cardioverter defibrillator leads (27.2 and 28.9 vs. 14.3%, P < 0.05). The groups were similar in the number of leads extracted per patient. Despite the increasing complexity of the systems extracted, complete extraction was achieved in a progressively greater proportion of leads (88.0% in Group 1, 95.5% in Group 2, and 97.6% in Group 3, P < 0.05), and procedure duration was similar. The proportion of leads for which femoral access was required was greater in Group 3 (11%, 18/164) compared with Group 2 (3%, 7/211), P = 0.006. The only major complications were a post-procedure subacute tamponade in Group 1 and an oesophageal injury related to transoesophageal echocardiography in Group 3. CONCLUSION: With current equipment, mechanical extraction provides a good combination of efficacy and safety.


Subject(s)
Cardiac Catheterization/methods , Defibrillators, Implantable , Device Removal/methods , Pacemaker, Artificial , Aged , Aged, 80 and over , Cardiac Catheterization/adverse effects , Cardiac Catheterization/instrumentation , Cardiac Catheterization/trends , Cardiac Catheters , Device Removal/adverse effects , Device Removal/instrumentation , Device Removal/trends , Diffusion of Innovation , Female , Humans , Male , Middle Aged , Patient Safety , Prosthesis Design , Prosthesis Failure , Risk Factors , Time Factors , Treatment Outcome
11.
J Behav Med ; 40(2): 249-258, 2017 Apr.
Article in English | MEDLINE | ID: mdl-27552993

ABSTRACT

We aimed to explore the combined contribution of pre-surgical depression and anxiety symptoms for recovery following coronary artery bypass graft (CABG) using data from 251 participants. Participants were assessed prior to surgery for depression and anxiety symptoms and followed up at 12 months to assess pain and physical symptoms, while hospital emergency admissions and death/major adverse cardiac events (MACE) were monitored on average 2.68 years after CABG. After controlling for covariates, baseline anxiety symptoms, but not depression, were associated with greater pain (ß = 0.231, p = 0.014) and greater physical symptoms (ß = 0.194, p = 0.034) 12 months after surgery. On the other hand, after controlling for covariates, baseline depression symptoms, but not anxiety, were associated with greater odds of having an emergency admission (OR 1.088, CI 1.010-1.171, p = 0.027) and greater hazard of death/MACE (HR 1.137, CI 1.042-1.240, p = 0.004). These findings point to different pathways linking mood symptoms with recovery after CABG surgery.


Subject(s)
Affect , Anxiety/psychology , Coronary Artery Bypass/psychology , Depression/psychology , Aged , Female , Hospitalization , Humans , Male , Middle Aged , Preoperative Period , Psychiatric Status Rating Scales , Recovery of Function
12.
Circ Res ; 115(10): 857-66, 2014 Oct 24.
Article in English | MEDLINE | ID: mdl-25201911

ABSTRACT

RATIONALE: Abdominal aortic aneurysms constitute a degenerative process in the aortic wall. Both the miR-29 and miR-15 families have been implicated in regulating the vascular extracellular matrix. OBJECTIVE: Our aim was to assess the effect of the miR-15 family on aortic aneurysm development. METHODS AND RESULTS: Among the miR-15 family members, miR-195 was differentially expressed in aortas of apolipoprotein E-deficient mice on angiotensin II infusion. Proteomics analysis of the secretome of murine aortic smooth muscle cells, after miR-195 manipulation, revealed that miR-195 targets a cadre of extracellular matrix proteins, including collagens, proteoglycans, elastin, and proteins associated with elastic microfibrils, albeit miR-29b showed a stronger effect, particularly in regulating collagens. Systemic and local administration of cholesterol-conjugated antagomiRs revealed better inhibition of miR-195 compared with miR-29b in the uninjured aorta. However, in apolipoprotein E-deficient mice receiving angiotensin II, silencing of miR-29b, but not miR-195, led to an attenuation of aortic dilation. Higher aortic elastin expression was accompanied by an increase of matrix metalloproteinases 2 and 9 in mice treated with antagomiR-195. In human plasma, an inverse correlation of miR-195 was observed with the presence of abdominal aortic aneurysms and aortic diameter. CONCLUSIONS: We provide the first evidence that miR-195 may contribute to the pathogenesis of aortic aneurysmal disease. Although inhibition of miR-29b proved more effective in preventing aneurysm formation in a preclinical model, miR-195 represents a potent regulator of the aortic extracellular matrix. Notably, plasma levels of miR-195 were reduced in patients with abdominal aortic aneurysms suggesting that microRNAs might serve as a noninvasive biomarker of abdominal aortic aneurysms.


Subject(s)
Aortic Aneurysm, Abdominal/blood , MicroRNAs/physiology , Aged , Animals , Aortic Aneurysm, Abdominal/metabolism , Aortic Aneurysm, Abdominal/pathology , Biomarkers/blood , Cells, Cultured , Humans , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , MicroRNAs/blood , Myocytes, Smooth Muscle/metabolism , Myocytes, Smooth Muscle/pathology
13.
Ann Behav Med ; 50(4): 545-53, 2016 08.
Article in English | MEDLINE | ID: mdl-26865259

ABSTRACT

BACKGROUND: Cognitive functioning is linked to cardiac mortality and morbidity, but the mechanisms underlying this relationship are unclear. PURPOSE: To examine the relationship between pre-operative cognitive functioning and post-operative inflammatory and neuroendocrine responses in patients undergoing coronary artery bypass graft (CABG) surgery. METHODS: One-hundred ninety-three outpatients were screened to assess their cognitive function using the Montreal Cognitive Assessment (MoCA) on average 30 days prior to CABG surgery and provided blood samples for the measurement of interleukin (IL)-6 and C-reactive protein (CRP) and saliva samples for the measurement of diurnal cortisol. Participants were followed-up 4-8 days following surgery for the repeat measurement of IL-6 and CRP and 60 days after surgery for the measurement of diurnal salivary cortisol. RESULTS: Patients with low cognitive function (MoCA < 26) prior to surgery reached higher IL-6 concentrations in the days after surgery (ß = -0.212, p = 0.021) and had greater cortisol output across the day 2 months after surgery (ß = -0.179, p = 0.044). CONCLUSIONS: Low cognitive functioning is associated with a more negative pattern of biological response to surgery, indicative of poorer physical recovery. These pathways may contribute to the links between cognitive function and cardiovascular pathology.


Subject(s)
C-Reactive Protein/metabolism , Cognition , Coronary Artery Bypass/psychology , Hydrocortisone/metabolism , Interleukin-6/blood , Aged , Female , Humans , Male , Postoperative Period , Preoperative Period , Saliva/metabolism
14.
J Behav Med ; 39(1): 120-7, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26341356

ABSTRACT

To determine the prospective association between health-related control beliefs, quality of life (QOL), depression symptoms, and health behaviours in coronary artery bypass graft (CABG) patients 6-8 weeks following surgery. 149 patients who were undergoing planned CABG surgery were recruited. Patients completed questionnaires measuring health related personal control, treatment control, depression symptoms, QOL, and health behaviours prior to and 6-8 weeks after surgery. Higher levels of health-related personal control predicted better QOL, and lower levels of depression symptoms, but not adherence to medication, cardiac rehabilitation attendance, or physical activity. These results were independent of demographic, behavioural, and clinical covariates. Treatment control was not associated with any outcome. These results suggest that perceived health-related personal control is associated with key aspects of short-term recovery from CABG surgery. Targeted interventions aimed at improving perceptions of health-related personal control may improve health outcomes in this cardiac population.


Subject(s)
Coronary Artery Bypass/psychology , Depression/psychology , Health Behavior , Internal-External Control , Quality of Life/psychology , Aged , Female , Health Status , Humans , Male , Middle Aged , Prospective Studies , Surveys and Questionnaires , Treatment Outcome
15.
J Cardiothorac Vasc Anesth ; 29(6): 1466-71, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26432698

ABSTRACT

OBJECTIVES: Fast-track (FT) management of cardiac surgery patients is associated with early extubation and reduced length of intensive care unit (ICU) stay, with potential benefit of reduced hospital costs. The authors examined perioperative factors and their influence on failure of FT and what implications this failure had. DESIGN: Prospective data collection from all adult cardiac surgeries between 2011 and 2013. SETTING: Single-institution study. PARTICIPANTS: The study included 2,770 consecutive adult cardiac surgery patients. INTERVENTIONS: All participants underwent adult cardiac surgeries. Of those, 451 (16.3%) patients were selected to undergo FT management. MEASUREMENTS AND MAIN RESULTS: Failure of FT was defined as early (admission to ICU on day of surgery) or late (patients later admitted to the ICU from the ward). Univariate and multivariate regression analyses were used to identify which variables predicted FT failure. Of the 451 patients included in this study, 138 (30.6%) failed the FT, with 115 (83.3%) early failures and 23 (16.7%) late failures. Predictors of failure were reduced renal function, hypertension, age, EuroSCORE, cardiopulmonary bypass time, first lactate or base deficit after surgery (all p<0.01), and cross-clamp time (p<0.05). Multivariate analysis showed that the strongest predictor of failure was glomerular filtration rate (GFR)<65 mL/min/BSA (sensitivity, 54%; specificity, 61%; likelihood ratio, 1.39; area under receiver operating characteristics curve, 0.59; 95% confidence interval, 0.53-0.64). Median length of hospital stay was longer for the failed group (5 v 7 days, p<0.001). There were no mortalities in any of the patients selected for FT. CONCLUSIONS: A number of perioperative factors are associated with failure to FT, the strongest predictor being GFR. Failure to FT can lead to significantly longer hospital stay.


Subject(s)
Cardiac Surgical Procedures/methods , Length of Stay/trends , Postoperative Care/methods , Preoperative Care/methods , Adolescent , Adult , Aged , Aged, 80 and over , Female , Glomerular Filtration Rate/physiology , Humans , Male , Middle Aged , Postoperative Complications/epidemiology , Postoperative Complications/prevention & control , Predictive Value of Tests , Prospective Studies , Time Factors , Treatment Failure , Young Adult
17.
Brain Behav Immun ; 37: 115-21, 2014 Mar.
Article in English | MEDLINE | ID: mdl-24239712

ABSTRACT

This study aimed to explore the role of C-reactive protein (CRP) in mediating the association between greater pre-operative depression symptoms and longer post-operative length of stay in patients undergoing coronary artery bypass graft (CABG) surgery. We used a sample of 145 elective CABG patients and measured depression symptoms using the Beck Depression Inventory (BDI) prior to surgery and collected baseline measures of CRP. Participants were followed up during their in-hospital stay to measure early (1-3 days post-surgery) and persistent (4-8 days post-surgery) CRP responses to surgery. We found that compared with participants with low depression symptoms, those with elevated depression symptoms (BDI>10) prior to CABG were at increased odds of a hospital stay of greater than one week (OR 3.51, 95% CI 1.415-8.693, p=0.007) and that greater persistent CRP responses mediated this association. Further work is needed to explore the exact physiological pathways through which depression and CRP interact to affect recovery in CABG patients.


Subject(s)
C-Reactive Protein/metabolism , Coronary Artery Bypass/psychology , Depression/metabolism , Depression/psychology , Length of Stay , Aged , Female , Humans , Male , Middle Aged
18.
Ann Behav Med ; 47(3): 347-57, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24272231

ABSTRACT

BACKGROUND: Sleep disturbance is associated with poorer outcomes in cardiac patients, but little is known about the independent role of sleep quality in coronary artery bypass graft (CABG) patients. PURPOSE: This study aims to examine the relationship between preoperative sleep complaints and post-operative emotional and physical recovery in CABG surgery patients, independently of demographic, clinical and mood factors. METHODS: Two hundred thirty CABG patients (aged 67.81 ± 9.07 years) completed measures of self-reported sleep complaints before surgery and health-related quality of life (HRQoL), physical symptoms and pain 2 months after surgery. RESULTS: Greater sleep complaints prior to surgery were associated with greater physical symptoms, poorer physical HRQoL and greater sensory pain after surgery (p < 0.05), but not with affective pain or mental HRQoL. Preoperative mood was not able to explain these associations. CONCLUSIONS: Sleep complaints may be implicated in physical recovery from CABG surgery but further work is needed to understand the role of causal pathways.


Subject(s)
Coronary Artery Bypass , Postoperative Complications/physiopathology , Postoperative Complications/psychology , Preoperative Period , Quality of Life/psychology , Sleep Wake Disorders/physiopathology , Sleep Wake Disorders/psychology , Affect , Aged , Coronary Artery Bypass/psychology , Female , Humans , Male , Pain/complications , Pain/psychology , Postoperative Period , Prospective Studies , Self Report , Symptom Assessment/psychology , Treatment Outcome
19.
Ann Thorac Surg ; 117(4): 669-689, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38284956

ABSTRACT

Enhanced Recovery After Surgery (ERAS) programs have been shown to lessen surgical insult, promote recovery, and improve postoperative clinical outcomes across a number of specialty operations. A core tenet of ERAS involves the provision of protocolized evidence-based perioperative interventions. Given both the growing enthusiasm for applying ERAS principles to cardiac surgery and the broad scope of relevant interventions, an international, multidisciplinary expert panel was assembled to derive a list of potential program elements, review the literature, and provide a statement regarding clinical practice for each topic area. This article summarizes those consensus statements and their accompanying evidence. These results provide the foundation for best practice for the management of the adult patient undergoing cardiac surgery.


Subject(s)
Cardiac Surgical Procedures , Enhanced Recovery After Surgery , Surgeons , Thoracic Surgery , Humans , Perioperative Care/methods , Cardiac Surgical Procedures/methods
20.
J Heart Valve Dis ; 22(2): 204-8, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23798209

ABSTRACT

BACKGROUND AND AIM OF THE STUDY: Surgical aortic valve replacement remains the 'gold standard' treatment for aortic valve disease. An increasing number of elderly patients with multiple comorbidities are referred for transcatheter aortic valve implantation (TAVI), partly due to the perceived high risks of surgery. These include in particular patients who have had previous cardiac surgery. The study aim was to compare the outcomes of patients with aortic valve disease and previous cardiac surgery who underwent TAVI, with those who had redo surgery. METHODS: Patients were identified with aortic valve disease and previous cardiac surgery referred to the authors' multidisciplinary meeting. Patient characteristics were noted, together with their allocation to either re-do surgery or TAVI. A total of 20 patients who had undergone previous cardiac surgery was allocated to TAVI; these were matched to 20 patients who had undergone previous surgery and subsequently had redo surgery. Treatment modalities were chosen for individual patients according to their EuroSCORE, together with other factors not accounted for in traditional scoring systems. RESULTS: Between June 2008 and March 2010, a total of 191 patients was discussed; of these patients, 63 underwent TAVI, 20 of whom had undergone previous cardiac surgery. There was no significant difference in the EuroSCORE between groups (18 +/- 2 versus 19 +/- 3.0, p = 0.91). TAVI patients had a higher body mass index (27.1 +/- 3.9 versus 21.8 +/- 0.5 kg/m2, p = 0.0001). There were no deaths at 30 days in either group. One patient (5%) in the TAVI group had a transient ischemic attack following the procedure, and one (5%) had a hematoma at the site of arterial puncture. There were more pacemaker implantations in the TAVI group than in the redo group (25% versus 0%, p = 0.02). CONCLUSION: Improved risk stratification and its understanding in patients with aortic valve disease and previous cardiac surgery is required. Despite the perceived high risks in the surgically treated group, there were no deaths and redo surgery patients had lower rates of stroke and pacemaker implantation than did those who underwent TAVI.


Subject(s)
Cardiac Catheterization/methods , Heart Defects, Congenital/surgery , Heart Valve Diseases/surgery , Heart Valve Prosthesis Implantation/methods , Aged , Aged, 80 and over , Aortic Valve/surgery , Bicuspid Aortic Valve Disease , Female , Humans , Male , Treatment Outcome
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