ANGPTL4 attenuates palmitic acid-induced endothelial cell injury by increasing autophagy.

ANGPTL4, a member of the angiopoietin-like protein family, is reported to be involved in angiogenesis regulation, lipid metabolism, glucose metabolism and redox reactions, among others. Our previous study showed that the plasma ANGPTL4 level was lower in coronary atherosclerotic heart disease (CAHD) and could be a useful predictor of coronary atherosclerosis. However, the molecular mechanism underlying the function of ANGPTL4 in atherosclerosis is poorly understood. In this study, we found that overexpression of ANGPTL4 in HUVECs enhanced cell proliferation and clone-forming ability in vitro, whereas knockdown of ANGPTL4 resulted in the opposite. The expression of ANGPTL4 was upregulated in palmitic acid (PA)-treated HUVECs. Overexpression of ANGPTL4 protected against PA-induced endothelial injury. Knockdown of ANGPTL4 exacerbated the effects of PA on HUVECs. Mechanistically, we demonstrated that ANGPTL4 promoted endothelial cell proliferation through the regulation of autophagy. Knockdown of ATG7 or 3-MA (an autophagy inhibitor) attenuated the effects of ANGPTL4 on endothelial cells. The serum level of ANGPTL4 was downregulated in atherosclerosis mice. Furthermore, the expression of ANGPTL4 was correlated with autophagy-related proteins in aortic tissues of atherosclerotic mice. ANGPTL4 promotes endothelial cell proliferation and suppresses PA-induced endothelial cell injury by increasing autophagy, which may protect against the development of atherosclerosis.

Circulating ANGPTL3 and ANGPTL4 levels predict coronary artery atherosclerosis severity.

BACKGROUND: We investigated the role of ANGPTL3 and ANGPTL4 in atherosclerosis development and determined whether plasma concentrations of ANGPTL3 and ANGPTL4 are related to the degree of coronary stenosis. METHODS: A total of 305 consecutive patients with angina who underwent diagnostic coronary angiography were enrolled in the study between August 2017 and August 2018. The levels of ANGPTL3 and ANGPTL4 were measured by using competitive ELISA kits. RESULTS: According to the degree of coronary artery stenosis, patients were classified into four types: coronary artery stenosis of < 10%, 10-50%, 50-75, and > 75%. The plasma ANGPTL3 level was higher (51.71 ± 52.67 vs. 24.65 ± 10.32 ng/mL, P < 0.001) and that of ANGPTL4 was lower (454.66 ± 269.05 vs. 875.49 ± 961.15 ng/mL, P < 0.001) in the coronary artery stenosis ≥ 10% group than in the < 10% group. ANGPTL3 and ANGPTL4 levels were significantly associated with the severity of coronary vascular stenosis. ROC curve analyses indicated that ANGPTL3 concentrations above 30.5 ng/mL can predict atherosclerosis with a sensitivity of 71.2% and specificity of 75.3%, and that ANGPTL4 levels below 497.5 ng/mL can predict atherosclerosis with a sensitivity of 63.9% and specificity of 74.5%. ANGPTL3 and ANGPTL4 were determined to be independent risk factors for coronary atherosclerosis with odds ratios (ORs) of 0.189 (95% CI 0.097-0.368, P < 0.001) and 3.625 (95% CI 1.873-7.016, P < 0.001), respectively. CONCLUSIONS: Increased ANGPTL3 or decreased ANGPTL4 shows an association with coronary atherosclerosis and, may become a predictor of coronary atherosclerosis in the future.

Novel PET/CT tracers for targeted imaging of membrane receptors to evaluate cardiomyocyte apoptosis and tissue repair process in a rat model of myocardial infarction.

The purpose of this study was to employ novel tracers PET imaging approach to define the time course and intensity of myocardial repair after apoptosis and to correlate the imaging signal to immunohistochemical staining in myocardial infarction (MI). We designed novel αVß3-targeted and radio-functionalized tracers for detection of apoptosis in H9C2 cells and myocardial tissue. MI rats were imaged with [18F]FDG, [18F]ANP-Cin or [18F]ANP-RGD2 using a small-animal PET/CT device. Rats were sacrificed, and tissue samples from viable and injured myocardial areas were sectioned for TUNEL assay and histology. The uncorrected radiochemical yield of [18F]ANP-Cin and [18F]ANP-RGD2 were 41.3 ± 5.4% and 21.17 ± 4.7%, respectively. Two tracers meet many criteria for cardiac imaging, including high stability, high binding, no toxicity, fast renal clearance and excellent biodistribution in rat models. The uptake of [18F]ANP-Cin was significantly higher on the 1st and 3rd day than the 7th or 28th day after MI induction, a timeframe associated with increased cardiomyocyte apoptosis. Higher uptake of [18F]ANP-Cin was observed in MI rats than in N-acetylcysteine (NAC)-treated rats on the 3rd days. In contrast with [18F]ANP-Cin, no hot-spots was observed with [18F]ANP-RGD2 on the 1st day and more hot-spots was observed from the 3rd day to the 7th day, then less on the 28th days in the high apoptotic site. There was no uptake of [18F]FDG in or around the apoptotic region. On the 7th day the uptake of [18F]ANP-RGD2 was higher in NAC-treated rats than MI rats. [18F]ANP-Cin and [18F]ANP-RGD2 are superior to [18F]FDG for PET/CT imaging for evaluation of cardiomyocyte apoptosis and tissue repair processes in the MI rats.