5 research outputs found
Hydrogen Sulfide Attenuates Atherosclerosis in a Partially Ligated Carotid Artery Mouse model via Regulating Angiotensin Converting Enzyme 2 Expression
No full textHydrogen Sulfide Attenuates Atherosclerosis in a Partially Ligated Carotid Artery Mouse model via Regulating Angiotensin Converting Enzyme 2 Expression
Full text linkHydrogen sulfide has been suggested to play an essential role in atherogenesis. There is a paucity of information about the association between H2S and angiotensin converting enzyme 2 (ACE2), a novel homolog of ACE. Therefore, the aim of the study was to explore the role of H2S in atherosclerosis with respect to ACE2 both in vitro and in vivo. Here, a murine model of acutely disturbed flow-induced atherosclerosis by left common carotid artery (LCA) partial ligation was utilized. We found that carotid partial ligation in high-fat fed apoE−/− mice significantly inhibited endogenous H2S synthesis in LCA. Application of NaHS, an H2S donor considerably attenuated the severity of atherosclerosis with upregulating carotid expression of ACE2, thus converting pro-atherosclerotic angiotensin II (Ang II) to anti-atherosclerotic angiotensin 1-7 (Ang-(1-7)). The anti-atherosclerotic effect of NaHS was dramatically abolished by treatment with MLN-4760, an ACE2 inhibitor. In contrast, blockage of H2S formation by DL-propargylglycine exacerbated the burden of atherosclerotic plaques accompanied by inhibiting carotid expression of ACE2. At the cellular level, NaHS dose-dependently promoted the expression of ACE2 and conversion from Ang II to Ang-(1-7) in unstimulated or LPS-stimulated endothelial cells, thus exerting anti-inflammatory properties. The anti-inflammatory effect of NaHS was abrogated by pretreatment with DX600, a selective ACE2 inhibitor. In conclusion, these data provide direct evidences that endogenous H2S insufficiency exists in acute flow disturbance-induced atherosclerosis and that application of H2S may protect against atherosclerosis via upregulating ACE2 expression in endothelial cells
Effect of GLP-1RA on coronary progression and cardiovascular outcomes in type 2 diabetic patients after PCI: a prospective cohort study
No full textAbstract Glucagon-like peptide-1 receptor agonists (GLP-1RAs) reduce incidence of cardiovascular events in type 2 diabetes (T2D) patients. Yet, the impact of GLP-1RAs on coronary lesion progression and cardiovascular outcomes after coronary stent implantation remains unclear. We aimed to investigate the effects of GLP-1RAs on coronary lesion progression and major adverse cardiovascular events (MACEs) after percutaneous coronary intervention (PCI). This prospective cohort study enrolled 1664 patients with T2D who underwent PCI from January 2020 to March 2024. Matched GLP-1RAs-treated and non-treated cohorts were formed using the propensity score matching method. The primary endpoint was the incidence of MACEs (cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, hospitalization for heart failure). Secondary endpoints included in-stent restenosis and non-target lesion progression. Two 131-patient cohorts with balanced baseline characteristics were formed by propensity score matching. During the median follow-up period of 20 months (ranging from 6 to 48 months), the incidence of MACEs was significantly lower in the GLP-1RA group (7.63%)compared to the control group (19.85%) (HR 0.444; 95%CI, 0.215–0.918; P = 0.024). During a median follow-up period of 12 months, 79.39% (104/131) of patients in the control group and 82.44% (108/131) of patients in the GLP-1RA group successfully underwent coronary angiography follow-up. The incidence of in-stent restenosis was 2.78% (3/108) in the GLP-1RA group and 11.54% (12/104) in the control group (P = 0.028). Non-target lesion progression was found in 10.19% (11/108) patient of the GLP-1RA group and 22.12% (23/104) in the control group (P = 0.037). Notable disparities were observed between the two groups regarding improvements of BMI, SBP, HbA1c, LDL-C, CRP. GLP-1RAs significantly reduced the incidence of MACEs and coronary lesion progression in patients with T2D after coronary stent implantation. These findings suggest that GLP-1RAs may have beneficial effects on cardiovascular outcomes and coronary artery disease progression in this population
MicroRNA-9 Inhibits NLRP3 Inflammasome Activation in Human Atherosclerosis Inflammation Cell Models through the JAK1/STAT Signaling Pathway
No full textBackground/Aims: MicroRNA-9 (miR-9) is involved in inflammatory reaction in atherosclerosis; however, its function and regulatory mechanisms remain unclear. We aimed to uncover the exact roles of miR-9 and downstream signaling pathways using in vitro human atherosclerosis models. Methods: We used oxidized low-density lipoprotein (oxLDL)-stimulated human THP-1 derived macrophages, oxLDL-stimulated human primary peripheral blood monocytes and lipopolysaccharides (LPS) or Alum-stimulated human THP-1 derived macrophages as in vitro atherosclerosis inflammation models. Transient transfection of over-expression vectors, small interference RNAs (siRNAs) or antisense oligonucleotides was used to regulate intracellular protein or miR-9 levels. Cell responses and signal transduction were detected by multiple assays including Western blotting, enzyme-linked immunosorbent assay (ELISA) and luciferase reporter assay. Results: MiR-9 inhibited while anti-miR-9 antisense oligonucleotides induced interleukin-1 beta (IL-1β) and NLRP3 inflammasome activation in all in vitro models. Janus kinase 1 (JAK1) and matrix metalloproteinase 13 (MMP-13) were identified as the target genes of miR-9. In oxLDL-stimulated human THP-1 derived macrophages, knockdown of JAK1 by siRNA blocked the phosphorylation of signal transducer and activator of transcription 1 (STAT1) and mimicked the effects of miR-9. In the same model, JAK1 knockdown blocked the phosphorylation of NF-κB p65 in the nuclei and the phosphorylation of NF-κB IκBα in the cytoplasm. Conclusions: Our study demonstrated that miR-9 could inhibit activation of the NLRP3 inflammasome and attenuate atherosclerosis-related inflammation, likely through the JAK1/STAT1 signaling pathway. Therefore, miR-9 may serve as a potential therapeutic target for atherosclerosis
Table_1_Association of Neutrophil to Lymphocyte Ratio With Plaque Rupture in Acute Coronary Syndrome Patients With Only Intermediate Coronary Artery Lesions Assessed by Optical Coherence Tomography.DOCX
No full textObjectivesPlaque vulnerability and rupture rather than plaque size are the major cause of clinical events in patients with intermediate coronary lesions. Therefore, the present study was aimed to explore potential markers associated with plaque rupture in acute coronary syndrome (ACS) patients with intermediate coronary lesions.MethodsA total of 82 ACS patients presenting with only intermediate coronary lesions (40–70% stenosis demonstrated by quantitative coronary angiography) and no severe stenosis in other main coronary arteries [median age 63 years, 53 male and 29 female] were enrolled. Plaque morphology were assessed by optical coherence tomography (OCT). Hematological indices were assayed by automated hematological analyzer.ResultsPlaque rupture was identified in 14 patients by OCT. Neutrophil to lymphocyte ratio (NLR) in patients with plaque rupture (n = 14) was significantly higher than that in patients with non-plaque rupture (n = 68) [3.85 (3.28, 4.77) vs. 2.13 (1.40, 2.81), p 2.94 for plaque rupture with 93.8% sensitivity and 77.9% specificity.ConclusionNLR, an inflammatory biomarker, is closely associated with plaque rupture in intermediate coronary artery lesions. Monitoring NLR may be useful in risk stratification and management for intermediate coronary artery lesions.</p
