Understanding the complex pathogenesis in myocardial ischemia/reperfusion (I/R) injury (IRI) is an urgent problem in clinical trials. Increasing pieces of evidence have suggested that miRNAs are involved in the occurrence and development of heart diseases by regulating mitochondria-related gene expression. Mitochondria have been acknowledged as the key triggers of cardiac I/R injury. However, the potential impact of miR-130a on mitochondria remains unclear in myocardial IRI. Exploring the regulatory mechanism of miR-130a on mitochondria may provide a new target for IRI therapy. In the present study, we found that miR-130a significantly increased in acute myocardial infarction (AMI) patients and myocardial I/R rats. MiR-130a could downregulate the viability of cardiomyocytes and the knockdown of miR-130a could protect the viability of cardiomyocytes under hypoxia-reoxygenation (HR). Over-expression of miR-130a resulted in mitochondrial dysfunction. It was evidenced by decreases in mitochondrial ATP production, mitochondrial membrane potential (MMP), and an increase in reactive oxygen species (ROS) production. However, suppression of miR-130a could protect against mitochondrial damage, show elevation of mitochondrial ATP production rate and MMP, and reduce ROS production. We further explored the effect of miR-130a on the mitochondrial quality control (QMC) system by determining mitochondrial-protein-specific proteases and analyzed mitochondrial morphology by fluorescence imaging and electron microscopy, respectively. It was noted that miR-130a could suppress mitochondrial fusion and FUNDC1-mediated mitophagy to accelerate myocardial IRI. Moreover, we investigated the potential miR-130a targeted mitochondria-related genes to understand the regulatory mechanism of miR-130a in the setting of myocardial IRI. It was revealed that miR-130a targeted GJA1, and GJA1 rescued IRI by enhancing ATP production rate and oxidative phosphorylation, meanwhile protecting cell viability, MMP, and activating mitophagy. In addition, the knockdown of miR-130a significantly activated FUNDC1-mediated mitophagy, while the knockdown of GJA1 reversed the relevant response. Collectively, our findings suggest that miR-130a regulates FUNDC1-mediated mitophagy by targeting GJA1 in myocardial IRI.
Background MHR is the ratio of monocyte to high-density lipoprotein cholesterol (HDL-C). It has been reported that MHR changes are associated with cardiovascular and cerebrovascular disease. Carotid plaque is a common vascular lesion of the carotid artery and is a manifestation of atherogenesis. This study investigated the relationships between the MHR and the incidence of carotid plaques. Methods The data of 3848 physical examiners were analyzed for retrospective analysis, which included 1428 patients with noncarotid plaque, 1133 patients with single carotid plaque, and 1287 patients with bilateral or multiple carotid plaques. Statistical analysis was performed on SPSS 22.0 0 software and statistical software R and its GAM package. Results The difference was statistically significant in the levels of MHR, body mass index (BMI), high-sensitivity C-reactive protein (hs-CRP), blood lipids (HDL-C, low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglyceride (Tg)), blood glucose (Glu), hemoglobin A1c (HbA1c), renal function (urea, creatinine (Crea)), estimated glomerular filtration rate (eGFR), and uric acid (Ua) in the carotid plaque groups (P < 0.001, respectively). There was no significant difference between the sex (P = 0.635) and age (P = 0.063) in the different groups. MHR levels were positively correlated with BMI (r = 0.364, P < 0.001), hs-CRP (r = 0.320, P < 0.001), Tg (r = 0.417, P < 0.001), Crea (r = 0.323, P < 0.001), eGFR (r = − 0.248, P < 0.001), Ua (r = 0.383, P < 0.001) and HbA1c (r = 0.197, P < 0.001). Levels of TC, Glu, and urea were slightly correlated with the MHR level (r = − 0.150, P < 0.001; r = 0.187, P < 0.001; r = 0.137, P < 0.001, respectively). The MHR level increased with elevated severity of carotid plaque in subjects without hypertension or diabetes (P < 0.001). In adjusted models, with the rise of MHR level, the probability of occurrence of carotid plaque had a 1.871-fold (95% CI: 1.015–3.450, P = 0.045) increase; the probability of multiple occurrences of carotid plaques had a 2.896-fold (95% CI: 1.415–5.928, P < 0.001) increase. The GAM curve showed a nonlinear correlation between the normalized MHR and the probability of carotid plaque occurrence. Conclusions MHR could be used as a possible marker for plaque formation and severity.
Background: Carotid plaque is a manifestation of carotid atherosclerosis,monocytes play a key role in atherosclerosis related inflammatory response ,high density lipoprotein cholesterol (HDL-C) has vascular protective effects such as anti-inflammatory, antithrombotic and anti atherosclerosis. This study is to investigate the relationships of MHR level and the incidence of carotid artery plaque. Methods: Data of physical examination personnel in the first medical center of the General Hospital of PLA from January to April in 2018 was collected and 3848 subjects were included for retrospectively analysis. Statistical analysis was performed on Spss 22.0 0 software and statistical software R and its GAM package.Results: The difference was statistically significant in levels of MHR, body mass index (BMI), high-sensitive C-reactive protein (hs-CRP), blood lipids (HDL-C, low-density lipoprotein cholesterol (LDL-C), total cholesterol(TC), triglyceride(Tg)), blood glucose(Glu), Hyperglycemic hemoglobin(HbA1c), renal function (Urea, creatinine(Crea), estimated glomerular filtration rate(eGFR), Uric acid (Ua)) in carotid plaque groups (p=0.000,respectively). No significant difference between the gender (p=0.635) and age(p=0.063) in different groups. MHR levels was positively correlated with levels of BMI (r = 0.364, P = 0.000), hs-CRP (r = 0.320, P =0.000), Tg (r = 0.417, P=0.000), Crea(r=0.323, P=0.000), eGFR(r=-0.248, P=0.000), Ua(r=0.383, P=0.000) and HbA1c (r=0.197, P=0.000). Levels of TC, Glu, Urea were slightly correlated with MHR level(r=-0.150, P=0.000; r=0.187, P=0.000; r=0.137, P=0.000; respectively ). In subjects with both hypertension and diabetes, MHR levels showed difference among three groups (p=0.009). MHR level increased with elevated site number of carotid plaque in subjects without hypertension or diabetes(p=0.000). MHR level still showed differences among carotid plaque groups in subjects with hypertension and diabetes. In adjusted models, the probability of occurrence of carotid plaque increased by1.958 (95% CI: 1.144-3.351, P = 0.000) times; The probability of multiple occurrence of carotid plaques increased by 2.068 (95% CI: 1.100-3.887, P = 0.000) times. The GAM curve showed a non-linear correlation between normalized MHR and the probability of carotid plaque occurrence. Conclusions: MHR could be used as an independent risk factor and indicator for plaque formation and severity.
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