A lanthanide-rich kilonova in the aftermath of a long gamma-ray burst.

Observationally, kilonovae are astrophysical transients powered by the radioactive decay of nuclei heavier than iron, thought to be synthesized in the merger of two compact objects1-4. Over the first few days, the kilonova evolution is dominated by a large number of radioactive isotopes contributing to the heating rate2,5. On timescales of weeks to months, its behaviour is predicted to differ depending on the ejecta composition and the merger remnant6-8. Previous work has shown that the kilonova associated with gamma-ray burst 230307A is similar to kilonova AT2017gfo (ref. 9), and mid-infrared spectra revealed an emission line at 2.15 micrometres that was attributed to tellurium. Here we report a multi-wavelength analysis, including publicly available James Webb Space Telescope data9 and our own Hubble Space Telescope data, for the same gamma-ray burst. We model its evolution up to two months after the burst and show that, at these late times, the recession of the photospheric radius and the rapidly decaying bolometric luminosity (Lbol ∝ t-2.7±0.4, where t is time) support the recombination of lanthanide-rich ejecta as they cool.

Optimizing transseptal puncture guided by three-dimensional mapping: the role of a unipolar electrogram in a needle tip.

AIMS: A three-dimensional electroanatomic mapping system-guided transseptal puncture (3D-TSP), without fluoroscopy or echocardiography, has been only minimally reported. Indications for 3D-TSP remain unclear. Against this background, this study aims to establish a precise technique and create a workflow for validating and selecting eligible patients for fluoroless 3D-TSP. METHODS AND RESULTS: We developed a new methodology for 3D-TSP based on a unipolar electrogram derived from a transseptal needle tip (UEGM tip) in 102 patients (the derivation cohort) with intracardiac echocardiography (ICE) from March 2018 to February 2019. The apparent current of injury (COI) was recorded at the muscular limbus of the foramen ovalis (FO) on the UEGM tip (sinus rhythm: 2.57 ± 0.95 mV, atrial fibrillation: 1.92 ± 0.77 mV), which then disappeared or significantly reduced at the central FO. Changes in the COI, serving as a major criterion to establish a 3D-TSP workflow, proved to be the most valuable indicator for identifying the FO in 99% (101/102) of patients compared with three previous techniques (three minor criteria) of reduction in atrial unipolar or bipolar potential and FO protrusion. A total of 99.9% (1042/1043) patients in the validation cohort underwent successful 3D-TSP through the workflow from March 2019 to July 2023. Intracardiac echocardiography guidance was required for 6.6% (69/1042) of patients. All four criteria were met in 740 patients, resulting in a 100% pure fluoroless 3D-TSP success rate. CONCLUSION: In most patients, fluoroless 3D-TSP was successfully achieved using changes in the COI on the UEGM tip. Patients who met all four criteria were considered suitable for 3D-TSP, while those who met none required ICE guidance.

Mapping and ablation of ventricular arrhythmias arising from the left ventricular summit.

The left ventricular summit (LVS) refers to the highest portion of the left ventricular outflow tract (LVOT). It is an epicardially delimited triangular area by the left coronary arteries and the coronary venous circulation. Its deep myocardium correlates closely with the left coronary cusp, aortic-mitral continuity, and right ventricular outflow tract (RVOT), complicating the anatomical relationship. Ventricular arrhythmias (VAs) originating from this area are common, accounting for 14.5% of all VAs origin from left ventricle. Specific electrocardiogram (ECG) characteristics may assist in locating LVS-VAs pre-procedure and facilitate procedure planning. However, catheter ablation of LVS-VAs remains challenging because of anatomical constraints. This paper reviews the recent understanding of LVS anatomy, concludes ECG characteristics, and summarizes current mapping and ablation methods for LVS-VAs.

Interplay of pro-inflammatory cytokines, pro-inflammatory microparticles and oxidative stress and recurrent ventricular arrhythmias in elderly patients after coronary stent implantations.

BACKGROUND: The roles of pro-inflammatory microparticles, pro-inflammatory cytokines and oxidative stress were unknown in elderly patients with recurrent ventricular arrhythmias (VA). We evaluated whether cross talk between oxidative stress, pro-inflammatory microparticles, and pro-inflammatory cytokines play the roles in elderly patients with recurrent VA after coronary stenting. This research sought to investigate the effects of oxidative stress, pro-inflammatory microparticles, and pro-inflammatory cytokines on recurrent VA in elderly patients after coronary stenting. METHODS: In this study, we included 613 consecutive elderly patients with recurrent ventricular arrhythmias induced by coronary reocclusions after coronary stenting. We measured CD31+ endothelial microparticle (CD31+EMP), CD62E+ endothelial microparticle (CD62E+EMP), high-sensitivity C-reactive protein (hs-CRP), aldosterone (ALD), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), soluble tumor necrosis factor receptor-1 (sTNFR-1) and soluble tumor necrosis factor receptor-2 (sTNFR-2) in elderly patients with recurrent VA and assessed impacts of pro-inflammatory microparticles, pro-inflammatory cytokines and oxidative stress on recurrent VA in elderly patients after coronary stenting. RESULTS: The levels of CD31+EMP, CD62E+EMP, hs-CRP, ALD, MDA, TNF-α, sTNFR-1 and sTNFR-2 were increased in recurrent malignant ventricular arrhythmia, sustained ventricular tachycardia, multiple ventricular premature beat and left and right ventricular bundle branch block groups (P < 0.001) in elderly patients with coronary reocclusions after coronary stent implantation. Upregulation of pro-inflammatory microparticles, pro-inflammatory cytokines and oxidative stress markers induced recurrent VA in elderly patients after coronary stenting. CONCLUSIONS: High levels of pro-inflammatory microparticles, pro-inflammatory cytokines and oxidative stress markers were associated with recurrent VA in elderly patients after coronary stenting. Our results suggested that the pro-inflammatory microparticles, pro-inflammatory cytokines and oxidative stress may simultaneously induce and aggravate recurrent VA in elderly patients after coronary stenting.

Serum miR-222 is independently associated with atrial fibrillation in patients with degenerative valvular heart disease.

BACKGROUND: Inflammation is involved in the progression of degenerative valvular heart disease (DVHD). microRNA-222 (miR-222) contributes to inflammation-mediated vascular remodeling, but its involvement in DVHD in relation to atrial fibrillation (AF) is unknown. This study aimed to investigate the changes in miR-222, interleukin (IL)-6, high-sensitivity C-reactive protein (hs-CRP), and N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with DVHD complicated with AF. METHODS: This was a case control study of patients with DVHD who were hospitalized at the Geriatrics Department of the Affiliated Huai'an Hospital of Xuzhou Medical University between 01/2017 and 08/2018. The participants were grouped according to the presence of AF, and serum miR-222, IL-6, hs-CRP, and NT-proBNP levels were compared. RESULTS: There were fifty-two participants (28 males) in the DVHD with AF group, aged 60-80 years (73.0 ± 5.9 years). Sixty participants (31 males) were included in the DVHD without AF group, aged 60-80 years (71.9 ± 6.92 years). There were no significant differences in age, sex, body mass index, fasting blood glucose, triglycerides, cholesterol, and blood pressure between the two groups. The serum levels of miRNA-222, IL-6, hs-CRP, and NT-proBNP in DVHD patients were significantly higher in those with AF compared with the non-AF group (all P < 0.05). Correlation analyses revealed that IL-6, hs-CRP, and NT-proBNP levels were positively correlated with miR-222 levels in all patients (IL-6: r = 0.507, P < 0.01; hs-CRP: r = 0.390, P < 0.01; NT-proBNP: r = 0.509, P < 0.01). CONCLUSIONS: Serum miR-222 was independently associated with AF in patients with DVHD.

Oxidative stress and inflammation: Early predictive indicators of multiple recurrent coronary in-stent chronic total occlusions in elderly patients after coronary stenting.

Pro-inflammatory responses and oxidative stress damages, and effects of the reduced anti-oxidation and anti-inflammation were involved in development and progression of coronary heart disease. We tried to identify the effects of pro-inflammatory and oxidative stress biomarkers as well as anti-oxidant and anti-inflammatory factors on multiple recurrent coronary in-stent chronic total occlusions in elderly patients after coronary stenting. We determined the expression levels of endothelial progenitor cell (EPC), stromal cell-derived factor-1α (SDF-1α), vascular endothelial growth factor (VEGF), nitric oxide (NO), toll-like receptor 2 (TLR2), toll-like receptor 3 (TLR3), toll-like receptor 4 (TLR4), and soluble ST2 (sST2) in elderly patients with multiple recurrent coronary in-stent chronic total occlusions after coronary stenting. The levels of EPC, SDF-1α, VEGF, and NO were decreased in elderly patients with multiple recurrent coronary in-stent chronic total occlusions (p < .001). The levels of TLR2, TLR3, TLR4, and sST2 were increased in elderly patients with multiple recurrent coronary in-stent chronic total occlusions (p < .001). The oxidative stress damages and pro-inflammatory responses played the crucial roles in multiple recurrent coronary in-stent chronic total occlusions of elderly patients after coronary stent placement. The levels of TLR2, TLR3, TLR4, and sST2, and the expressions of EPC, SDF-1α, VEGF, and NO could be considered as potential early predictive indicators for multiple recurrent coronary in-stent chronic total occlusions in elderly patients after coronary stent implantation.

Pro-inflammatory cytokines, oxidative stress and diffuse coronary reocclusions in elderly patients after coronary stenting.

BACKGROUND: The inflammation responses and oxidative stress were closely associated with coronary heart disease. We tried to evaluate the effects of multiple stents, long stents and small-diameter stents on inflammation responses and oxidative stress in the elderly patients with long diffuse reocclusions. METHODS: The blood samples were obtained after an overnight fast and we evaluated the expression levels of soluble ST2 (sST2), acrolein (ACR), aldosterone (ALD), angiotensin II (Ang II), toll-like receptor 4 (TLR4), tumour necrosis factor-α (TNF-α), malondialdehyde (MDA) and high sensitivity C-reactive protein (hs-CRP) in the elderly patients with long diffuse reocclusions after multiple stents, long stents, small-diameter stents implanted. RESULTS: Levels of sST2, ACR, ALD, Ang II, TLR4, TNF-α, MDA and hs-CRP were remarkably increased (P < 0.001) in the elderly patients with long diffuse reocclusions after multiple stents, long stents, small-diameter stents implanted. The multiple stents, long stents and small-diameter stents may promote inflammatory response and oxidative stress, and led to long diffuse reocclusions in the elderly patients. The multiple stents, long stents and small-diameter stents may play the key roles in long diffuse reocclusions of the elderly patients. CONCLUSIONS: The inflammatory and oxidative stress biomarkers could be considered as potential non-invasive diagnostic, predictive, prognostic and therapeutic molecular biomarkers for long diffuse reocclusions in the elderly patients after implantations of multiple stents, long stents and small-diameter stents.

Interplay of TNF-α, soluble TNF receptors and oxidative stress in coronary chronic total occlusion of the oldest patients with coronary heart disease.

BACKGROUND: The interplay of tumour necrosis factor-α (TNF-α) and oxidative stress was related to severities of coronary atherosclerosis and congestive heart failure. We tried to identify TNF-α, soluble tumour necrosis factor-α receptor-1 (sTNFR-1), soluble tumour necrosis factor-α receptor-2 (sTNFR-2) and oxidative stress as potential non-invasive diagnostic and therapeutic biomarkers for coronary chronic total occlusion (CCTO) in the oldest patients with coronary heart disease (CHD). METHODS: We determined the expression levels of TNF-α, sTNFR-1, sTNFR-2, oxidative stress biomarkers (malondialdehyde [MDA], aldosterone [ALD], angiotensin II [Ang II], and high sensitivity C-reactive protein [hs-CRP]) in oldest patients with CCTO. RESULTS: The levels of TNF-α, sTNFR-1, sTNFR-2, MDA, ALD, Ang II and hs-CRP were increased in oldest patients with CCTO (P < 0.001). The CCTO of oldest patients with CHD may involve the interplay of TNF-α, sTNFR-1, sTNFR-2 and oxidative stress. CONCLUSIONS: The TNF-α, sTNFR-1, sTNFR-2 and oxidative stress could be considered as potential non-invasive diagnostic and therapeutic biomarkers for CCTO in the oldest patients with CHD.

Effects of Altered Levels of Pro- and Anti-Inflammatory Mediators on Locations of In-Stent Reocclusions in Elderly Patients.

Imbalances of proatherogenic inflammatory and antiatherogenic inflammatory mediators were involved in the pathogenesis of atherosclerosis. This study sought to investigate the effects of proatherogenic inflammatory and antiatherogenic inflammatory mediators on the proximal, middle, and distal coronary artery reocclusions in elderly patients after coronary stent implantations. We measured the expression levels of proatherogenic inflammatory/antiatherogenic inflammatory cytokines. This included interleukin-1 ß (IL-1 ß), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α), high-sensitivity C-reactive protein (hs-CRP), interleukin-10 (IL-10), interleukin-17 (IL-17), interleukin-13 (IL-13), and interleukin-37 (IL-37) in the elderly patients with the proximal, middle, and distal coronary artery reocclusions after coronary stent implantations. Levels of IL-1 ß, IL-6, IL-8, TNF-α, and hs-CRP were remarkably increased (P < 0.001), and levels of IL-10, IL-17, IL-13, and IL-37 were remarkably lowered (P < 0.001) in the elderly patients with the proximal, middle, and distal coronary artery reocclusions. Imbalances of proatherogenic inflammatory and antiatherogenic inflammatory mediators may be involved in the formation and progression of proximal, middle, and distal coronary artery reocclusions in elderly patients after coronary stent implantations.

Side Effects of Coronary Stenting such as Severe Coronary Stenosis and Multiple Coronary Chronic Total Occlusions in Elderly Patients via Induced Proinflammatory and Prooxidative Stress.

BACKGROUND: Severe coronary stenosis and multiple coronary chronic total occlusions are serious side effects of coronary stent implantation in elderly patients. This research sought to investigate the side effects of coronary stenting such as severe coronary stenosis and multiple coronary chronic total occlusions in elderly patients via induced proinflammatory and prooxidative stress. METHODS: We evaluated the expression levels of tumor necrosis factor-α (TNF-α), toll-like receptor 4 (TLR4), acrolein (ACR), malondialdehyde (MDA), high-sensitivity C-reactive protein (hs-CRP), stromal cell-derived factor-1α (SDF-1α), superoxide dismutase 3 (SOD3), and endothelial nitric oxide synthase (eNOS) in elderly patients with severe coronary stenosis and multiple coronary chronic total occlusions. RESULTS: Levels of TNF-α, TLR4, ACR, MDA, and hs-CRP were remarkably increased (P < 0.001), and levels of SDF-1α, SOD3, and eNOS were remarkably lowered (P < 0.001) in elderly patients with severe coronary stenosis and multiple coronary chronic total occlusions. Coronary stenting induced proinflammatory and prooxidant mediator expression and inhibited anti-inflammatory/antioxidant mediators. The proinflammatory and prooxidant mediators may be involved in severe coronary stenosis and multiple coronary chronic total occlusions in elderly patients. CONCLUSIONS: Side effects such as severe coronary stenosis and multiple coronary chronic total occlusions because of coronary stenting in elderly patients were induced by proinflammatory and prooxidative stress. Circulating proinflammatory and prooxidant mediators could predict early severe coronary stenosis and multiple coronary chronic total occlusions in elderly coronary heart disease patients.

Roles of MDA-LDL/OX-LDL/LOX-1 and TNF-α/TLR4/NF-κB Signaling Pathways in Myocardial Damage by Implantations of Cardiac Pacemakers in Elderly Patients.

INTRODUCTION: Permanent pacemakers are an established treatment for sick sinus syndrome and high-grade atrioventricular block. Permanent cardiac pacemaker implantations may damage the myocardium. OBJECTIVE: This study evaluated markers of myocardial injury, oxidative stress and inflammation in elderly patients with permanent pacemaker implantations. METHODS: Various markers were measured at 1, 2, 3 and 4 months after permanent pacemaker implantations in elderly patients. RESULTS: The levels of high-sensitivity troponin T (hsTnT), lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), malondialdehyde-modified low-density lipoprotein (MDA-LDL), oxidized low-density lipoprotein (OX-LDL), tumour necrosis factor-α (TNF-α), toll-like receptor 4 (TLR4) and nuclear factor-kappa B (NF-κB) were increased in 2-month group compared with control and 1- month groups (P<0.001), and were further increased at 4-month group compared with 2- and 3- month groups after pacemaker implantations (P<0.001). Patients with dual-chamber pacemakers had higher levels of hsTnT, LOX-1, MDA-LDL, OX-LDL, TNF-α, TLR4 and NF-κB than patients with single chamber pacemakers (P<0.001). Patients who underwent the pacemakers with the active fixation leads had raised levels of hsTnT, LOX-1, MDA-LDL, OX-LDL, TNF-α, TLR4 and NF-κB compared patients with pacemakers using the passive fixation leads (P<0.001). Myocardial blood flows in 3-month and 4-month groups were lower than 1-month and 2-month groups (P<0.001). CONCLUSION: Levels of hsTnT, LOX-1, MDA-LDL, OX-LDL, TNF-α, TLR4 and NF-κB were elevated in elderly patients with permanent pacemaker implantations and the activations of oxidative stress and pro-inflammatory signalling pathways may be associated with myocardial damages and ischemia after pacemaker implantations in elderly patients.

Signaling Pathways (TNF-α-NF-κB, TLR2-TLR4 as well as ROS-MDA) and Cardiac Damages during Cardiac Surgeries (Coronary stenting, Permanent Pacemaker Implantations, Radiofrequency Ablations).

INTRODUCTION: The mutual activations of multiple signaling pathways are the key factors in the development and progression of myocardial cell injuries. OBJECTIVE: This research aimed to compare the different degrees of myocardial injury after coronary stenting, permanent pacemaker implantations, or cardiac radiofrequency ablation and to investigate the effects of the mutual activation of TNF-α/NF-κB, TLR2/TLR4, and ROS/MDA signaling pathways on myocardial injury in elderly patients after coronary stents or permanent pacemakers or radiofrequency ablation. METHODS: We determined reactive oxygen species (ROS), malondialdehyde (MDA), toll-like receptor 2 (TLR2), toll-like receptor 4 (TLR4), nuclear factor kappa B (NF-κB), tumor necrosis factor- α (TNF-α) and high-sensitive cardiac troponin T (hs-cTnT) as a marker of myocardial injury in patients. RESULTS: The levels of ROS, MDA, TLR2, TLR4, NF-κB, TNF-α, and hs-cTnT were increased in patients with permanent pacemaker implantations when compared to patients with cardiac radiofrequency ablation (P < 0.01) at 6 months and were further increased in patients with coronary stenting compared to patients with cardiac radiofrequency ablation and permanent pacemaker implantations at 6 months, respectively (P < 0.01). This research confirmed that ROS, MDA, TLR2, TLR4, NF-κB, and TNF-α predicted myocardial injury severity. CONCLUSION: Oxidative stress (ROS/MDA signaling pathway) may be linked to immune response (TLR2/TLR4 signaling pathway) and pro-inflammatory response (TNF-α/NF-κB signaling pathway) in myocardial injury, and ROS/MDA signaling may play a dominant role.

Interplay between Pro-inflammatory Mediators and Oxidative Stressinvolved Recurrent Chronic Heart Failure in Elderly Patients with Coronary Stents.

INTRODUCTION: Inflammation and oxidative stress are related to congestive heart failure in patients with coronary heart disease. OBJECTIVE: Chronic congestive heart failure is a serious stage of coronary artery disease and is mainly a disease of elderly people over the age of 65. Elderly heart failure patients are characterized by myocardial ischemia, and post-ischemic myocardial dysfunction. Oxidative Stress, inflammation, and immune response play important roles in the development of heart failure. We tried to examine the mutual triggering of oxidative stress (malondialdehyde), inflammatory cytokines (tumor necrosis factor-α and soluble tumor necrosis factor receptor-1/2), immune response (toll-like receptors 2,3,4), and high sensitivity C-reactive protein expression in elderly patients with recurrent congestive heart failure after coronary stenting and investigated the effect of interplay of these changes on onset and progression of recurrent congestive heart failure in elderly patients underwent coronary stent implantation. METHODS: A total of 726 patients were enrolled in this study. We determined the levels of malondialdehyde (MDA), high sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF- α), soluble tumor necrosis factor receptor-1 and 2 (sTNFR-1/2) and toll-like receptor 2,3,4 (TLR2/3/4) in elderly patients with recurrent congestive heart failure after coronary artery stent implantation. RESULTS: Levels of MDA, hs-CRP, TNF-α, sTNFR-1, sTNFR-2, TLR2, TLR3 and TLR4 were remarkably increased (p<0.01) in elderly patients with recurrent congestive heart failure after coronary artery stenting. The results indicated that these markers were closely correlated to each other and showed that these markers were associated with increased New York Heart Association functional classification and low left ventricular ejection fractions. Further analysis confirmed that the independent clinical risk factors for recurrent congestive heart failure were MDA, hs-CRP, TNF-α, sTNFR-1, sTNFR-2, TLR2, TLR3 and TLR4. The interplay of oxidative stress, inflammatory cytokines and toll-like receptors, and hs-CRP expression levels was an important factor involved in recurrent congestive heart failure of elderly patients after coronary stenting. CONCLUSION: High levels of MDA, hs-CRP, TNF-α, sTNFR-1, sTNFR-2, TLR2, TLR3 and TLR4 had an important implication for recurrent heart failure with increased New York Heart Association functional classification and low left ventricular ejection fractions. These eight factors amplified each other's positive effects and this interaction may be a key element of their roles in recurrent heart failure. The eight risk factors were inter-dependent and occurred simultaneously, and exerted detrimental effects forming a vicious circle. MDA may trigger the over-expressions of pro-inflammatory risk factors (hs-CRP, TNF-α, sTNFR-1, sTNFR-2) through the activation of TLRs as risk factors (TLR2, TLR3 and TLR4) contributing to the dysfunction of myocardial mitochondria, cardiomyocyte hypertrophy, maladaptive myocardial remodeling, myocardial interstitial fibrosis, cardiac systolic decrease and recurrent heart failure. These eight risk factors were the basis of the mechanisms of recurrent heart failure. Therefore, the mutual triggering of oxidative stress, inflammatory and toll-like receptor signaling pathways, and hs-CRP expression could play key roles in the development of recurrent congestive heart failure in elderly patients after coronary stenting.

Cardiac Radiofrequency Ablation Exacerbates Myocardial Injury through Pro-Inflammatory Response and Pro-Oxidative Stress in Elderly Patients with Persistent Atrial Fibrillation.

BACKGROUND: There is a need to assess myocardial damage after radiofrequency ablation of the pulmonary veins (PV) for persistent atrial fibrillation (PAF) in elderly patients. OBJECTIVE: To evaluate oxidative stress, inflammatory response and myocardial damage in elderly patients with PAF after radiofrequency ablation of the PV. METHODS: High-sensitivity troponin T (hsTnT), malondialdehyde-modified low-density lipoprotein (MDA-LDL), acrolein (ACR), lipid hydroperoxide (LHP), toll-like receptor 4 (TLR4), soluble growth stimulation expressed gene 2 (sST2), angiotensin II (Ang II) and myocardial blood flow (MBF) were determined before ablation and at 1, 3 and 5 months after radiofrequency ablation. RESULTS: The levels of hsTnT, MDA-LDL, ACR, LHP, TLR4, sST2 and Ang II were increased 3 months after ablations compared with before ablation and 1 month after ablation, respectively (P<0.001); they were further increased at 5 months after ablation compared with the 1- and 3-month groups, respectively (P<0.001). MBF was decreased in the 3 months group after ablations compared with before ablation and 1-month after ablation, respectively (P<0.001), and was further decreased in 5-months after ablations compared with 1-month and 3-month groups, respectively (P<0.001). Patients with epicardial monopolar radiofrequency ablation had higher levels of hsTnT, MDA-LDL, ACR, LHP, TLR4, sST2, Ang II and lower MBF than patients with endocardial monopolar and bipolar radiofrequency ablations, respectively (P<0.001). CONCLUSION: Monopolar radiofrequency ablation method could result in more myocardial injury than bipolar radiofrequency ablation. Oxidative stress and inflammatory response may be involved in cardiac radiofrequency ablation-induced myocardial injury, resulting in myocardial ischemia in elderly patients with PAF.

Pro-Inflammatory Signaling Cascade Markers, Oxidative Stress-Inflammatory Signaling Axis, and Chronic Total Occlusion of Tibial Artery in Elderly Patients Suffering from Occlusion of Coronary Arteries.

INTRODUCTION: Oxidative response is a risk factor in the progression of arterial atherosclerosis. OBJECTIVE: This research study aimed to examine the effects of oxidative response on atherosclerotic susceptibility as well as the development of arteriosclerosis occlusions of the tibial artery through pro-inflammatory mediator genes in elderly patients with occlusion of coronary arteries. METHODS: We determined that oxidative stress biomarkers (Malondialdehyde-modified Low-density Lipoprotein (MDA-LDL), Oxidized Low-density Lipoprotein (Ox-LDL) as well as Heme Oxygenase- 1 (HO-1)] and the expressions of pro-inflammatory mediator genes [Toll-like Receptor 4 (TLR4), Nuclear Factor kappa-B (NF-κB), Myeloid Differentiating factor 88 (MyD88) and Growth Arrest-specific gene 6 (GAS6)] have an impact on the severity of arteriosclerosis occlusions of tibial artery in elderly patients suffering from occlusion of coronary arteries. RESULTS: Levels of MDA-LDL, Ox-LDL, HO-1, TLR4, NF-κB, MyD88, and GAS6 were increased in the occlusion of tibial arteries + two-vessel coronary occlusion group compared to the CON group and occlusion of tibial arteries + one-vessel coronary occlusion group, respectively (p < 0.001); they were also elevated in occlusion of tibial arteries + multiple-vessel coronary occlusion group compared to occlusion of tibial arteries + one-vessel coronary occlusion group and occlusion of tibial arteries + two-vessel coronary occlusion group, respectively (P < 0.001). This has indicated the key roles of oxidative stress and pro-inflammatory mediator genes in arteriosclerosis occlusions of tibial artery in elderly patients with occlusion of coronary arteries. CONCLUSION: Oxidative response may promote the expressions of inflammatory genes and enhance susceptibility to arteriosclerosis occlusions of the tibial artery in elderly patients with chronic total coronary occlusions.

Oxidative Stress and Inflammation Markers Associated with Multiple Peripheral Artery Occlusions in Elderly Patients.

Background: Pro-oxidative stress and pro-inflammatory responses can influence each other in the development of atherosclerosis. This study evaluated the relationship between oxidative stress, inflammation, and multiple peripheral artery occlusions in elderly patients (age mean 71.2 ± 8.1 years). Methods: A total of 723 participants were enrolled: 67 healthy subjects, 214 patients with common iliac artery occlusions, 224 patients with popliteal artery occlusions, and 218 patients with femoral artery occlusions. We measured oxidative stress biomarkers (malondialdehyde [MDA], F2-isoprostane [F2-isoP], total oxidant status [TOS], and ischemia-modified albumin [IMA]) and the expressions of molecules in mimecan (MIME)/nuclear factor kappa B (NF-κB)/P53/Toll-like receptor 4 (TLR4) signaling pathway in older patients with multiple peripheral artery occlusions. Results: The levels of MDA, F2-isoP, TOS, IMA, MIME, NF-κB, P53, and TLR4 were increased in the single-site peripheral artery occlusive group when compared with healthy controls (P < .001) and were further increased in the multiple-site peripheral artery occlusive group compared with the single-site peripheral artery occlusive group (P < .001). Conclusion: Oxidative stress may promote inflammatory signaling pathways and lead to multiple peripheral artery occlusions in elderly patients.

Potential Biomarkers and Therapeutic Targets: Inflammation and Oxidative Stress in Left Carotid Artery Stenosis with Coronary Artery Disease.

INTRODUCTION: Patients with left carotid artery atherosclerotic stenosis have an increased ischemic stroke risk. Left carotid stenosis, the most common cause of the transient ischemic attack, is related to a higher risk of acute stroke. Left carotid artery stenosis is also associated with cerebral artery infarction. The significant coronary stenosis promotes ST-segment elevation myocardial infarctions. The severe coronary stenosis plays an important role in development and progression of myocardial infarction. However, the dynamic changes of circulating oxidative stress and inflammatory markers in the carotid stenosis combined with coronary artery stenosis are not clear, and it also remains unknown whether mark of oxidative stress and inflammation are potential therapeutic targets for carotid stenosis combined with coronary artery stenosis. AIM: This study aims to explore the effects of oxidative stress combined with an inflammatory response on left carotid artery stenosis with coronary artery disease in patients. METHODS: We, therefore, tested the hypothesis that levels of markers of oxidative stress and inflammation are associated with coexistent severe carotid and coronary artery stenosis in patients. We measured the circulating levels of malondialdehyde (MDA), oxidized low-density lipoprotein (OX-LDL), homocysteine (Hcy), F2- isoprostanes (F2-IsoPs), tumor necrosis factor-alpha (TNF-α), high-sensitivity C-reactive protein (hs-CRP), prostaglandin E2 (PG-E2) and interferon-gamma (IFN-γ) in patients with combined carotid and coronary artery severe stenosis. We also assessed the relationships among oxidative stress, inflammation, and severe stenosis of the carotid with a coronary artery in patients. RESULTS: Levels of MDA, OX-LDL, Hcy, F2-IsoPs, TNF-α, hs-CRP, PG-E2, and IFN-γ were remarkably increased (P < 0.001) in patients with combined carotid and coronary artery severe stenosis. High levels of oxidative stress and inflammation may be related to severe stenosis of the carotid with coronary arteries in patients. CONCLUSION: Our observations indicated that measurements of oxidative stress and inflammatory markers may be valuable for the assessment of the degree of carotid with coronary artery stenosis. The biomarkers of oxidative stress and inflammatory response may become therapeutic targets for carotid artery stenosis with coronary artery stenosis in patients.

Mechanism exploration of 6-Gingerol in the treatment of atherosclerosis based on network pharmacology, molecular docking and experimental validation.

BACKGROUND: The 6-Gingerol has significant anti-inflammatory, anti-oxidative and hypolipidemic activities and is widely used for treating cardiac-cerebral vascular diseases. However, the multi-target mechanism of 6-Gingerol in the treatment of atherosclerosis remains to be elucidated. METHODS: Firstly, the therapeutic actions of 6-Gingerol anti-atherosclerosis were researched based on an atherosclerotic ApoE-deficient mice model induced by high-fat feed. Then, network pharmacology and molecular docking were employed to reveal the anti-atherogenic mechanism of 6-Gingerol. Finally, the target for these predictions was validated by target protein expression assay in vitro and in vivo experiments and further correlation analysis. RESULTS: Firstly, 6-Gingerol possessed obvious anti-atherogenic activity, which was manifested by a significant reduction in the plaque area, decrease in the atherosclerosis index and vulnerability index. Secondly, based on network pharmacology, 14 predicted intersection target genes between the targets of 6-Gingerol and atherogenic-related targets were identified. The key core targets of 6-Gingerol anti-atherosclerosis were found to be TP53, RELA, BAX, BCL2, and CASP3. Lipid and atherosclerosis pathways might play a critical role in 6-Gingerol anti-atherosclerosis. Molecular docking results also further revealed that the 6-Gingerol bound well and stable to key core targets from network pharmacological predictions. Then, the experimental results in vivo and in vitro verified that the up-regulation of TP53, RELA, BAX, CASP3, and down-regulation of BCL2 from atherosclerotic ApoE-deficient mice model can be improved by 6-Gingerol intervention. Meanwhile, the correlation analysis further confirmed that 6-Gingerol anti-atherosclerosis was closely related to these targets. CONCLUSION: The 6-Gingerol can markedly improve atherosclerosis by modulating key multi-targets TP53, RELA, BAX, CASP3, and BCL2 in lipid and atherosclerosis pathways. These novel findings shed light on the anti-atherosclerosis mechanism of 6-Gingerol from the perspective of multiple targets and pathways.

Evaluation of Oxidative Status in Elderly Patients with Multiple Cerebral Infarctions and Multiple Chronic Total Coronary Occlusions.

Background: Oxidative stress plays a key role in atherosclerosis. Acting via high level of reactive oxygen species, an increase of oxidative stress is involved in the pathogenesis and progression of atherosclerostic stenosis or occlusion of arteries. Oxidative stress leads to an accumulation of oxidized low-density lipoprotein, which plays important roles in steno-occlusion of cerebral and coronary arteries. However, the exact reasons for multiple cerebral and coronary artery steno-occlusion in elderly patients remain unclear. The aim was to evaluate the effects of imbalance of oxidative/antioxidative status on concomitant multiple brain infarcts and multiple chronic total coronary occlusions in elderly patients. Methods: We measured the circulating levels of malondialdehyde (MDA), reactive oxygen species (ROS), thiobarbituric acid reactive substance (TBARS), advanced oxidation protein products (AOPP), superoxide dismutase 1 (SOD 1), superoxide dismutase 2 (SOD 2), superoxide dismutase 3 (SOD 3), and paraoxonase 1 (PON 1) in patients with concomitant multiple cerebral infarcts and multiple chronic total coronary occlusions. Results: Circulating levels of oxidative stress markers (MDA, ROS, TBARS, and AOPP) were increased (P < 0.001) and antioxidative stress markers (SOD 1, SOD 2, SOD 3, and PON 1) were decreased (P < 0.001) in elderly patients with concomitant multiple brain infarcts and multiple chronic total coronary occlusions. Conclusions: The findings suggested that the imbalance of oxidative/antioxidative status may be associated with multiple cerebral infarcts and multiple chronic total coronary occlusions and may contribute to the development of concomitant multiple brain infarcts and multiple chronic total coronary occlusions in elderly patients.

Toll-Like Receptors/TNF-α Pathway Crosstalk and Impact on Different Sites of Recurrent Myocardial Infarction in Elderly Patients.

Background: Recurrent myocardial infarction is associated with increased mortality. Risk and predictive factors of recurrent myocardial infarction in elderly patients after coronary stenting are not well known. This research sought to investigate the effects of proinflammatory cytokines and toll-like receptor on recurrent myocardial infarction after coronary stenting in elderly patients. Methods: We measured the levels of toll-like receptor 2 (TLR2), toll-like receptor 3 (TLR3), toll-like receptor 4 (TLR4), tumor necrosis factor-α (TNF-α), soluble tumor necrosis factor-α receptor-1 (sTNFR-1), soluble tumor necrosis factor-α receptor-2 (sTNFR-2), endothelial progenitor cells (EPCs), and vascular endothelial growth factor (VEGF) in elderly patients with recurrent myocardial infarction and assessed the changes of proinflammatory cytokines and toll-like receptors in elderly patients with recurrent myocardial infarction after coronary stenting. Results: Levels of TLR2, TLR3, TLR4, TNF-α, sTNFR-1, and sTNFR-2 were remarkably increased (P < 0.001), and EPCs and VEGF were remarkably lowered (P < 0.001) in the elderly patients with recurrent myocardial infarction after coronary stent implantation. Increased expressions of proinflammatory cytokines and toll-like receptors induced recurrent myocardial infarction after coronary stenting. Elevated expressions of proinflammatory cytokines and toll-like receptors may be used to identify elderly patients who have an increased risk of developing recurrent myocardial infarction after coronary stenting. Conclusion: The increase levels of proinflammatory cytokines and toll-like receptors were associated with recurrent myocardial infarction after coronary stenting. Increased expressions of proinflammatory cytokines and toll-like receptors may be clinically useful biomarkers for predicting recurrent myocardial infarction in the elderly patients after coronary stent implantation.