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1.
South Med J ; 116(11): 848-856, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37913802

RESUMO

OBJECTIVES: A comprehensive cardiovascular disease (CVD) prevention approach should address patients' medical, behavioral, and psychological issues. The aim of this study was to understand the clinician-reported availability of a pertinent CVD preventive workforce across various specialties using a survey study in the southeastern United States, an area with a disproportionate burden of CVD and commonly known as the Stroke Belt. METHODS: We surveyed physicians, advanced practice providers (APPs), and pharmacists in internal medicine, family medicine, endocrinology, and cardiology regarding available specialists in CVD preventive practice. We examined categorical variables using the χ2 test and continuous variables using the t test/analysis of variance. RESULTS: A total of 263 clinicians from 21 health systems participated (27.6% response rate, 91.5% from North Carolina). Most were women (54.5%) and physicians (72.5%) specializing in cardiology (43.6%) and working at academic centers (51.3%). Overall, most clinicians stated having adequate specialist services to manage hypertension (86.6%), diabetes mellitus (90.1%), and dyslipidemia (84%), with >50% stating having adequate specialist services for obesity, smoking cessation, diet/nutrition, and exercise counseling. Many reported working with an APP (69%) or a pharmacist (56.5%). Specialist services for exercise therapy, psychology, behavioral counseling, and preventive cardiology were less available. When examined across the four specialties, the majority reported having adequate specialist services for hypertension, diabetes mellitus, obesity, dyslipidemia, and diet/nutrition counseling. Providers from all four specialties were less likely to work with exercise therapists, psychologists, behavioral counselors, and preventive cardiologists. CONCLUSIONS: A majority of providers expressed having adequate specialists for hypertension, diabetes mellitus, dyslipidemia, obesity, smoking cessation, diet/nutrition, and exercise counseling. Most worked together with APPs and pharmacists but less frequently with exercise therapists, psychologists, behavioral counselors, and preventive cardiologists. Further research should explore approaches to use and expand less commonly available specialists for optimal CVD preventive care.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus , Dislipidemias , Hipertensão , Humanos , Feminino , Estados Unidos/epidemiologia , Masculino , Hipertensão/epidemiologia , Hipertensão/prevenção & controle , Obesidade , Medicina de Família e Comunidade , North Carolina , Doenças Cardiovasculares/prevenção & controle
2.
Tex Heart Inst J ; 50(1)2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36695737

RESUMO

A 67-year-old woman experienced pruritus, an urticarial rash, and acute, pressure-like chest pain following an insect sting. Initial electrocardiographic findings were notable for ST-segment elevations in the inferior leads without reciprocal changes, but a follow-up electrocardiogram showed pronounced ST-segment elevations in the inferior leads with reciprocal changes. Her troponin I level peaked at 3,053 pg/mL, and she was transferred to a large academic center for percutaneous coronary intervention. Balloon angioplasty was performed for 95% thrombotic occlusion of the mid-right coronary artery, and a drug-eluting stent was placed. The patient's presentation was consistent with type II Kounis syndrome.


Assuntos
Angioplastia Coronária com Balão , Stents Farmacológicos , Síndrome de Kounis , Feminino , Humanos , Idoso , Síndrome de Kounis/diagnóstico , Síndrome de Kounis/etiologia , Síndrome de Kounis/terapia , Coração , Eletrocardiografia
3.
Eur J Clin Nutr ; 77(1): 112-115, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35986210

RESUMO

BACKGROUND: Recent evidence has shown associations between cardiovascular disease and a proinflammatory diet. We hypothesized that a proinflammatory diet, assessed using the Empirical Dietary Inflammatory Index (EDII), is associated with increased risk of prevalent heart failure (HF). METHODS: This analysis included 13,687 participants (44.8 ± 19.4 years; 45.7% male, 67.8% whites) from the Third National Health and Nutrition Examination Survey. EDII score was calculated from the Food Frequency Questionnaire. Prevalent HF was determined by physician-diagnosed self-report. Multivariable logistic regression analysis was used to calculate odds ratios (OR) and 95% confidence intervals (CI) for the association between EDII score and prevalent HF across tertiles (reference group first tertile) and per 1-unit standard deviation (1-SD) increase. RESULTS: About 1.4% (n = 190) of the participants reported a history of HF. Each 1-SD increase in EDII score (0.276) conferred 25% increased odds of prevalent HF (OR (95% CI): 1.25 (1.07-1.46); p value = 0.006). Odds of HF increased as EDII tertile increased, indicating a dose-response relationship (OR (95% CI) for 2nd and 3rd tertiles compared to 1st tertile: 1.42 (0.99-2.04), 1.68 (1.15-2.46), respectively). These results were consistent in subgroups of the participants stratified by demographics and comorbidities. CONCLUSIONS: Proinflammatory dietary patterns are associated with an increased risk of HF. The risk of HF could potentially be reduced by avoiding proinflammatory dietary patterns.


Assuntos
Dieta , Insuficiência Cardíaca , Humanos , Masculino , Adulto , Estados Unidos/epidemiologia , Feminino , Inquéritos Nutricionais , Dieta/efeitos adversos , Comorbidade , Inquéritos e Questionários , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/etiologia , Fatores de Risco
4.
Curr Hypertens Rep ; 24(12): 723-733, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36350493

RESUMO

PURPOSE OF REVIEW: We reviewed the effects of hypertension and the means to prevent and treat it across the spectrum of a woman's lifespan and identified gaps in sex-specific mechanisms contributing to hypertension in women that need to be addressed. RECENT FINDINGS: Hypertension continues to be an important public health problem for women across all life stages from adolescence through pregnancy, menopause, and older age. There remain racial, ethnic, and socioeconomic differences in hypertension rates not only overall but also between the sexes. Blood pressure cutoffs during pregnancy have not been updated to reflect the 2017 ACC/AHA changes due to a lack of data. Additionally, the mechanisms behind hypertension development in menopause, including sex hormones and genetic factors, are not well understood. In the setting of increasing inactivity and obesity, along with an aging population, hypertension rates are increasing in women. Screening and management of hypertension throughout a women's lifespan are necessary to reduce the burden of cardiovascular disease, and further research to understand sex-specific hypertension mechanisms is needed.


Assuntos
Doenças Cardiovasculares , Hipertensão , Gravidez , Adolescente , Masculino , Animais , Feminino , Humanos , Idoso , Hipertensão/epidemiologia , Menopausa , Doenças Cardiovasculares/prevenção & controle , Estágios do Ciclo de Vida , Envelhecimento
5.
Case Reports Immunol ; 2022: 7971169, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36277471

RESUMO

Vasculitic immune checkpoint inhibitor-related adverse events (irAEs) are rare, with limited data to guide their management. Here, we present a case of a 67-year-old female with stage IV cutaneous melanoma who received first-line pembrolizumab. She had completed 21 cycles of pembrolizumab dosed at 200 mg every 21 days over 15 months when she developed fatigue, chills, decreased appetite, night sweats, nausea, diarrhea, dry cough, and chest pain. A routine, staging positron emission tomography (PET) scan revealed aortitis of the transverse aortic arch. An extensive workup was unremarkable for other causes, so her condition was labeled a grade III immune-related vasculitis. Based on this diagnosis, we started high-dose prednisone and discontinued pembrolizumab. After two months of high-dose prednisone, she developed bothersome weight gain and insomnia, leading to a switch from prednisone to tocilizumab as a steroid-sparing agent. The selection of tocilizumab was based on its routine use for giant cell arteritis which can have extracranial symptoms including thoracic aortitis. Her symptoms resolved, and subsequent PET scans showed resolution of the aortitis and no evidence of metastatic melanoma. As the indications for immunotherapy expand, rare complications are becoming more prevalent, and more data will be needed to guide their management. While there is evidence for tocilizumab use as a steroid-sparing treatment for large-vessel vasculitides due to other conditions, this is the first case of its use to treat an aortitis irAE to our knowledge. In this case, it was an effective means of treating the patient while sparing them from prolonged corticosteroids.

7.
Tex Heart Inst J ; 48(4)2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34652434

RESUMO

During the coronavirus disease 2019 (COVID-19) pandemic, social distancing guidelines have negatively affected the care-seeking behavior of patients with chronic medical conditions, including those with cardiovascular disease. We report the case of a 60-year-old man with vague gastrointestinal symptoms who waited more than 1 week to seek treatment for fear of COVID-19 infection. On presentation at another hospital, he was found to have had an anterior myocardial infarction, and he underwent percutaneous coronary intervention to stent an occluded proximal left anterior descending coronary artery. Subsequently, the patient experienced refractory cardiogenic shock and, during his transfer to our hospital, refractory ventricular tachycardia, which ultimately proved fatal.


Assuntos
COVID-19 , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Medo , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/efeitos adversos , SARS-CoV-2 , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia
8.
Infect Dis (Lond) ; 53(8): 633-639, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33905273

RESUMO

BACKGROUND: Endocarditis during pregnancy carries a maternal mortality of up to 30%, but prior publications do not reflect the current opioid epidemic. CASE PRESENTATIONS: We reviewed our institution's infective endocarditis registry from 2009 to 2019 and identified 19 females with endocarditis during pregnancy in order to compare our contemporary outcomes with historical reports. In our cohort, intravenous drug use was reported in all cases, and the most common pathogen was Staphylococcus (74%) followed by Serratia (13%). The tricuspid valve was involved in 18 (95%) patients, and contrary to prior reports, all but two patients were managed conservatively with antibiotics alone. Maternal and infant mortality (5% and 0%, respectively) were lower in our cohort compared to all previous reviews. CONCLUSION: We conclude that the better outcomes seen in this report are likely due to the younger age of the patients and the more frequent right-sided valvular involvement. SUMMARY: This review highlights contemporary outcomes in endocarditis during pregnancy. We review historical case reports in light of the opioid epidemic. We observed more Staphylococcus, more right-sided valvular involvement, and more conservative management as well as improved maternal and foetal mortality.


Assuntos
Endocardite Bacteriana , Endocardite , Preparações Farmacêuticas , Abuso de Substâncias por Via Intravenosa , Endocardite/tratamento farmacológico , Endocardite/epidemiologia , Endocardite Bacteriana/tratamento farmacológico , Endocardite Bacteriana/epidemiologia , Feminino , Humanos , Gravidez , Abuso de Substâncias por Via Intravenosa/complicações , Valva Tricúspide
9.
J Thromb Thrombolysis ; 51(1): 217-225, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32542527

RESUMO

PERTs are a new, multidisciplinary approach to PE care. They were conceived to efficiently identify and risk stratify PE patients and standardize care delivery. More research needs to be conducted to assess the effects that PERTs have had on PE care. This study sought to determine the effects of a PERT on quality and overall value of care. This was a retrospective study of all patients 18 years of age or older who presented with a principal diagnosis of an acute PE based on available ICD codes from January 1, 2010 to December 31, 2018. Patients who did not have an imaging study, i.e., CTPA or ECHO, available were excluded. Patients were divided into pre- (before October 2015) and post-PERT eras (after October 2015) and stratified based on the presence of right heart strain/dysfunction on imaging. All quality outcomes were extracted from the EMR, and cost outcomes were provided by the financial department. 530 individuals (226 pre-PERT and 304 post-PERT) were identified for analysis. Quality outcomes improved between the eras; most notably in-hospital mortality decreased (16.5 vs. 9.6) and hospital LOS decreased (7.7 vs. 4.4) (p < 0.05). Total cost of care also decreased a statistically significant amount between the eras. The implementation of a PERT improved quality and cost of care, resulting in improved value. We hypothesize that this may be due to more timely identification and risk stratification leading to earlier interventions and streamlined decision making, but further research is required to validate these findings in larger cohorts.


Assuntos
Embolia Pulmonar/diagnóstico , Medição de Risco , Adulto , Idoso , Atenção à Saúde/economia , Mortalidade Hospitalar , Humanos , Pessoa de Meia-Idade , Equipe de Assistência ao Paciente/economia , Prognóstico , Embolia Pulmonar/economia , Embolia Pulmonar/mortalidade , Estudos Retrospectivos , Medição de Risco/economia
10.
Shock ; 54(6): 738-743, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32826822

RESUMO

OBJECTIVES: We investigated whether platelet count associated with biomarkers of endothelial function, and additionally sought to identify novel predictors of outcomes in a cohort of patients with severe sepsis at a quaternary care academic medical center. DESIGN: Prospective, observational cohort. PATIENTS: Eighty-six sepsis patients admitted into intensive care units were prospectively enrolled into an on-site sepsis registry and biobank. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Platelet count, mean platelet volume, platelet mass, plasma angiopoietin-1 and angiopoietin-2, syndecan-1, platelet factor 4, sCD40L concentrations, and plasma autotaxin activity were determined for each patient at enrollment. Patient mortality was recorded up to 30 days following hospital discharge. Platelet count and plasma sCD40L was significantly lower in patients who did not survive up to 30 days following hospital discharge. Angiopoietin-2 and the angiopoietin-2/1 ratio were significantly higher in patients who did not survive up to 30 days following discharge. Furthermore, plasma autotaxin activity was significantly higher in patients who did not survive up to 30 days. Interestingly, autotaxin activity correlated with platelet count and the ratio of angiopoietin-2/1 across our population. CONCLUSIONS: Platelet count, the ratio of angiopoietin-2/1, and autotaxin activity all predicted 30-day mortality. Autotaxin activity within the plasma correlates with both platelet counts and vascular dysfunction biomarkers across both survivors and non-survivors indicating a possible involvement of autotaxin within sepsis.


Assuntos
Diester Fosfórico Hidrolases/sangue , Sistema de Registros , Sepse , Adulto , Idoso , Angiopoietina-1/sangue , Angiopoietina-2/sangue , Biomarcadores/sangue , Intervalo Livre de Doença , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Estudos Prospectivos , Sepse/sangue , Sepse/mortalidade , Sepse/terapia , Taxa de Sobrevida , Fatores de Tempo
11.
Circulation ; 141(13): 1080-1094, 2020 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-31941367

RESUMO

BACKGROUND: Myocardial infarction (MI) triggers myelopoiesis, resulting in heightened production of neutrophils. However, the mechanisms that sustain their production and recruitment to the injured heart are unclear. METHODS: Using a mouse model of the permanent ligation of the left anterior descending artery and flow cytometry, we first characterized the temporal and spatial effects of MI on different myeloid cell types. We next performed global transcriptome analysis of different cardiac cell types within the infarct to identify the drivers of the acute inflammatory response and the underlying signaling pathways. Using a combination of genetic and pharmacological strategies, we identified the sequelae of events that led to MI-induced myelopoiesis. Cardiac function was assessed by echocardiography. The association of early indexes of neutrophilia with major adverse cardiovascular events was studied in a cohort of patients with acute MI. RESULTS: Induction of MI results in rapid recruitment of neutrophils to the infarct, where they release specific alarmins, S100A8 and S100A9. These alarmins bind to the Toll-like receptor 4 and prime the nod-like receptor family pyrin domain-containing 3 inflammasome in naïve neutrophils and promote interleukin-1ß secretion. The released interleukin-1ß interacts with its receptor (interleukin 1 receptor type 1) on hematopoietic stem and progenitor cells in the bone marrow and stimulates granulopoiesis in a cell-autonomous manner. Genetic or pharmacological strategies aimed at disruption of S100A8/A9 and their downstream signaling cascade suppress MI-induced granulopoiesis and improve cardiac function. Furthermore, in patients with acute coronary syndrome, higher neutrophil count on admission and after revascularization correlates positively with major adverse cardiovascular disease outcomes. CONCLUSIONS: Our study provides novel evidence for the primary role of neutrophil-derived alarmins (S100A8/A9) in dictating the nature of the ensuing inflammatory response after myocardial injury. Therapeutic strategies aimed at disruption of S100A8/A9 signaling or their downstream mediators (eg, nod-like receptor family pyrin domain-containing 3 inflammasome, interleukin-1ß) in neutrophils suppress granulopoiesis and may improve cardiac function in patients with acute coronary syndrome.


Assuntos
Calgranulina A/metabolismo , Granulócitos/metabolismo , Infarto do Miocárdio/sangue , Neutrófilos/metabolismo , Animais , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Camundongos
12.
Resusc Plus ; 4: 100039, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34223316

RESUMO

AIM OF THE STUDY: Most survivors of an in-hospital cardiac arrest do not leave the hospital alive, and there is a need for a more patient-centered, holistic approach to the assessment of prognosis after an arrest. We sought to identify pre-, peri-, and post-arrest variables associated with in-hospital mortality amongst survivors of an in-hospital cardiac arrest. METHODS: This was a retrospective cohort study of patients ≥18 years of age who were resuscitated from an in-hospital arrest at our University Medical Center from January 1, 2013 to September 31, 2016. In-hospital mortality was chosen as a primary outcome and unfavorable discharge disposition (discharge disposition other than home or skilled nursing facility) as a secondary outcome. RESULTS: 925 patients comprised the in-hospital arrest cohort with 305 patients failing to survive the arrest and a further 349 patients surviving the initial arrest but dying prior to hospital discharge, resulting in an overall survival of 29%. 620 patients with a ROSC of greater than 20 min following the in-hospital arrest were included in the final analysis. In a stepwise multivariable regression analysis, recurrent cardiac arrest, increasing age, time to ROSC, higher serum creatinine levels, and a history of cancer were predictors of in-hospital mortality. A history of hypertension was found to exert a protective effect on outcomes. In the regression model including serum lactate, increasing lactate levels were associated with lower odds of survival. CONCLUSION: Amongst survivors of in-hospital cardiac arrest, recurrent cardiac arrest was the strongest predictor of poor outcomes with age, time to ROSC, pre-existing malignancy, and serum creatinine levels linked with increased odds of in-hospital mortality.

13.
Stem Cell Rev Rep ; 14(5): 702-714, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29948752

RESUMO

BACKGROUND: Acute myocardial infarction (MI) and the ensuing ischemic heart disease are approaching epidemic state. Unfortunately, no definitive therapies are available and human regenerative therapies have conflicting results. Limited stem cell retention following intracoronary administration has reduced the clinical efficacy of this novel therapy. Cathelicidin related antimicrobial peptides (CRAMPs) enhance chemotactic responsiveness of BMSPCs to low SDF-1 gradients, suggesting a potential role in BMSPCs engraftment. Here, we assessed the therapeutic efficacy of CRAMPs in the context of BMSPCs recruitment and retention via intracardiac delivery of CRAMP-treated BMSPCs or CRAMP-releasing hydrogels (HG) post-AMI. METHODS: For cell transplantation experiments, mice were randomized into 3 groups: MI followed by injection of PBS, BMMNCs alone, and BMMNCs pre-incubated with CRAMP. During the in vivo HG studies, BM GFP chimera mice were randomized into 4 groups: MI followed by injection of HG alone, HG + SDF-1, HG + CRAMP, HG + SDF-1 + CRAMP. Changes in cardiac function at 5 weeks after MI were assessed using echocardiography. Angiogenesis was assessed using isolectin staining for capillary density. RESULTS: Mice treated with BMMNCs pre-incubated with CRAMP had smaller scars, enhanced cardiac recovery and less adverse remodeling. Histologically, this group had higher capillary density. Similarly, sustained CRAMP release from hydrogels enhanced the therapeutic effect of SDF-1, leading to enhanced functional recovery, smaller scar size and higher capillary density. CONCLUSION: Cathelicidins enhance BMMNC retention and recruitment after intramyocardial administration post-AMI resulting in improvements in heart physiology and recovery. Therapies employing these strategies may represent an attractive method for improving outcomes of regenerative therapies in human studies.


Assuntos
Peptídeos Catiônicos Antimicrobianos/administração & dosagem , Transplante de Medula Óssea , Infarto do Miocárdio/terapia , Medicina Regenerativa , Animais , Peptídeos Catiônicos Antimicrobianos/metabolismo , Modelos Animais de Doenças , Humanos , Leucócitos Mononucleares/metabolismo , Leucócitos Mononucleares/transplante , Masculino , Camundongos , Infarto do Miocárdio/fisiopatologia , Retenção Psicológica/efeitos dos fármacos , Catelicidinas
14.
J Crit Care ; 44: 261-266, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29220755

RESUMO

PURPOSE: Sepsis is a highly prevalent and fatal condition, with reported cardiovascular event rates as high as 25-30% at 1year. Risk stratification in septic patients has been extremely limited. MATERIAL AND METHODS: 267 septic patients with detectable troponin levels, APACHE II scores, and CT scans of the chest or abdomen were assessed. Patients with a recent cardiac intervention were excluded. Coronary artery calcification (CAC) was identified as present or absent on body CT scans. Cardiovascular death, acute myocardial infarction (AMI), or PCI at 1year was assessed using multivariate logistic regression analysis. RESULTS: Patients with CAC were older, predominantly male with more risk factors for coronary disease, but similar peak troponin levels and APACHE II scores. In a multivariate analysis, CAC was predictive of the primary outcome (OR 6.827; 95% CI 1.336-54.686; p=0.037). Patients with no CAC, history of CHF or CKD were at low risk (<1%) for cardiovascular complications at 1year even at very high troponin levels (<8.0ng/dL). CONCLUSION: CAC risk stratifies septic patients for cardiovascular complications better than traditional risk factors and can be identified on body CT scans. This novel, risk stratifying framework built on CAC can help guide individualized management of septic patients.


Assuntos
Doença da Artéria Coronariana/complicações , Vasos Coronários/patologia , Sepse/complicações , Calcificação Vascular/complicações , Calcificação Vascular/patologia , Idoso , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/fisiopatologia , Vasos Coronários/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Fatores de Risco , Sepse/metabolismo , Sepse/fisiopatologia , Tomografia Computadorizada por Raios X , Troponina/metabolismo , Calcificação Vascular/diagnóstico por imagem , Calcificação Vascular/fisiopatologia
15.
Stem Cells Transl Med ; 4(11): 1333-43, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26371341

RESUMO

UNLABELLED: Acute myocardial infarction (AMI) triggers mobilization of bone marrow (BM)-derived stem/progenitor cells (BMSPCs) through poorly understood processes. Recently, we postulated a major role for bioactive lipids such as sphingosine-1 phosphate (S1P) in mobilization of BMSPCs into the peripheral blood (PB). We hypothesized that elevating S1P levels after AMI could augment BMSPC mobilization and enhance cardiac recovery after AMI. After AMI, elevating bioactive lipid levels was achieved by treating mice with the S1P lyase inhibitor tetrahydroxybutylimidazole (THI) for 3 days (starting at day 4 after AMI) to differentiate between stem cell mobilization and the known effects of S1P on myocardial ischemic pre- and postconditioning. Cardiac function was assessed using echocardiography, and myocardial scar size evolution was examined using cardiac magnetic resonance imaging. PB S1P and BMSPCs peaked at 5 days after AMI and returned to baseline levels within 10 days (p < .05 for 5 days vs. baseline). Elevated S1P paralleled a significant increase in circulating BMSPCs (p < .05 vs. controls). We observed a greater than twofold increase in plasma S1P and circulating BMSPCs after THI treatment. Mechanistically, enhanced BMSPC mobilization was associated with significant increases in angiogenesis, BM cell homing, cardiomyocytes, and c-Kit cell proliferation in THI-treated mice. Mice treated with THI demonstrated better recovery of cardiac functional parameters and a reduction in scar size. Pharmacological elevation of plasma bioactive lipids after AMI could contribute to BMSPC mobilization and could represent an attractive strategy for enhancing myocardial recovery and improving BMSC targeting. SIGNIFICANCE: Acute myocardial infarction (AMI) initiates innate immune and reparatory mechanisms through which bone marrow-derived stem/progenitor cells (BMSPCs) are mobilized toward the ischemic myocardium and contribute to myocardial regeneration. Although it is clear that the magnitude of BMSPC mobilization after AMI correlates with cardiac recovery, the molecular events driving BMSPC mobilization and homing are poorly understood. The present study confirms the role of bioactive lipids in BMSPC mobilization after AMI and proposes a new strategy that improves cardiac recovery. Inhibiting sphingosine-1 phosphate (S1P) lyase (SPL) allows for the augmentation of the plasma levels of S1P and stem cell mobilization. These findings demonstrate that early transient SPL inhibition after MI correlates with increased stem cell mobilization and their homing to the infarct border zones. Augmenting BMSPC mobilization correlated with the formation of new blood vessels and cardiomyocytes and c-Kit cell proliferation. These novel findings on the cellular level were associated with functional cardiac recovery, reduced adverse remodeling, and a decrease in scar size. Taken together, these data indicate that pharmacological elevation of bioactive lipid levels can be beneficial in the early phase after cardiac ischemic injury. These findings provide the first evidence that a carefully timed transient pharmacological upregulation of bioactive lipids after AMI could be therapeutic, because it results in significant cardiac structural and functional improvements.


Assuntos
Células da Medula Óssea/metabolismo , Inibidores Enzimáticos/farmacologia , Mobilização de Células-Tronco Hematopoéticas , Lisofosfolipídeos/sangue , Proteínas de Membrana/antagonistas & inibidores , Infarto do Miocárdio , Monoéster Fosfórico Hidrolases/antagonistas & inibidores , Esfingosina/análogos & derivados , Células-Tronco/metabolismo , Animais , Biomarcadores/sangue , Células da Medula Óssea/patologia , Modelos Animais de Doenças , Imidazóis/farmacologia , Proteínas de Membrana/metabolismo , Camundongos , Infarto do Miocárdio/sangue , Infarto do Miocárdio/patologia , Infarto do Miocárdio/terapia , Monoéster Fosfórico Hidrolases/metabolismo , Esfingosina/sangue , Células-Tronco/patologia
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