Search

Doxorubicin (DOX) has a wide antitumor spectrum, but its adverse cardiotoxicity may lead to heart failure. Urotensin II (UII) is the most potent vasoconstrictor in mammals. It plays a role by activating the UII receptor (UT), the orphan G protein-coupled receptor (GPR14), collectively referred to as the UII/UT system. In the new version of "Chinese expert consensus on cardiac rehabilitation of chronic heart failure," it is pointed out that exercise rehabilitation is the cornerstone of cardiac rehabilitation. In this study, in vitro and in vivo assessments were performed using DOX-treated H9C2 cells and rats. It was found that the UT antagonist Urantide and exercise training improved DOX-induced cardiac insufficiency, reduced DOX-induced cardiomyocyte apoptosis, improved the structural disorder of myocardial fibers, and inhibited DOX-induced myocardial fibrosis. Further studies showed that Urantide alleviated DOX-induced cardiotoxicity by downregulating the expression levels of the p38 mitogen-activated protein kinase signaling pathway. [ABSTRACT FROM AUTHOR]

• Homocysteine promoted HASMC proliferation and up-regulated linc-ROR expression. • Linc-ROR promoted the proliferation and migration of HASMCs. • Linc-ROR acted as a competing endogenous RNA for miR-195-5p. • Linc-ROR-mediated HASMC proliferation and migration may be via regulating miR-195-5p/FGF2 axis. Atherosclerosis is a common cardiovascular disorder and is characterized by damage of endothelial cells, cell inflammation, hyper-proliferation of vascular smooth muscle cells and the accumulation of extracellular lipids and fibrous tissues. In this study, we firstly examined the expression level of long intergenic non-protein coding RNA, regulator of reprogramming (linc-ROR) in homocysteine (Hcy)-stimulated human aortic smooth muscle cells (HASMCs), and then looked into the potential molecular signaling axis of linc-ROR in regulating the proliferation and migration of HASMCs. Hcy promoted HASMC proliferation and up-regulated linc-ROR expression. Functional studies showed that linc-ROR exerted enhanced actions on the proliferation and migration of HASMCs. In addition, linc-ROR acted as a competing endogenous RNA for miR-195-5p and repressed the miR-195-5p expression in HASMCs. Linc-ROR was up-regulated the miR-195-3p was down-regulated in the plasma from CAD patients when compared to normal controls. Furthermore, fibroblast growth factor 2 (FGF2) was identified as a target of miR-195-5p and was negatively regulated by miR-195-5p in HASMCs. The rescue experiments revealed that linc-ROR-mediated HASMC proliferation and migration may be via regulating miR-195-5p/FGF2 axis. Linc-ROR inhibition blocked the miR-195-5p/FGF2 signaling in Hcy-treated HASMCs, and this effect may also involve in the miR-195-5p/FGF2 axis. To summarize, the data of the present study identified the up-regulation of linc-ROR in Hcy-stimulated HASMCs, and further mechanistic functional studies revealed that linc-ROR promoted HASMC proliferation and migration via regulating miR-195-5p/FGF2 axis. The present study provided the novel actions of linc-ROR in regulating HASMC proliferation and migration, which may be related to the pathophysiology of atherosclerosis. [ABSTRACT FROM AUTHOR]

Background: The available evidence regarding the benefits of percutaneous coronary intervention (PCI) on patients receiving dialysis with coronary artery disease (CAD) is limited and inconsistent. This study aimed to evaluate the association between PCI and clinical outcomes as compared with medical therapy alone in patients undergoing dialysis with CAD in China., Methods: This multicenter, retrospective study was conducted in 30 tertiary medical centers across 12 provinces in China from January 2015 to June 2021 to include patients on dialysis with CAD. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Secondary outcomes included all-cause death, the individual components of MACE, and Bleeding Academic Research Consortium criteria types 2, 3, or 5 bleeding. Multivariable Cox proportional hazard models were used to assess the association between PCI and outcomes. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for potential between-group differences., Results: Of the 1146 patients on dialysis with significant CAD, 821 (71.6%) underwent PCI. After a median follow-up of 23.0 months, PCI was associated with a 43.0% significantly lower risk for MACE (33.9% [ n  = 278] vs . 43.7% [ n  = 142]; adjusted hazards ratio 0.57, 95% confidence interval 0.45-0.71), along with a slightly increased risk for bleeding outcomes that did not reach statistical significance (11.1% vs . 8.3%; adjusted hazards ratio 1.31, 95% confidence interval, 0.82-2.11). Furthermore, PCI was associated with a significant reduction in all-cause and cardiovascular mortalities. Subgroup analysis did not modify the association of PCI with patient outcomes. These primary findings were consistent across IPTW, PSM, and competing risk analyses., Conclusion: This study indicated that PCI in patients on dialysis with CAD was significantly associated with lower MACE and mortality when comparing with those with medical therapy alone, albeit with a slightly increased risk for bleeding events that did not reach statistical significance., (Copyright © 2024 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)

Background: With the extensive application of stent implantation in patients undergoing percutaneous coronary interventions (PCI), there are chances that in-stent restenosis (ISR)-a major vascular complication caused by vascular smooth muscle cell (VSMC) phenotypic transformation-might occur., Objectives: This study sought to evaluate the role of lincRNA-POU3F3 on VSMC phenotypic transformation and the underlying mechanism., Methods: VSMCs were used in our research. We first constructed a gene delivery system through an assembly of lipofectamine and a functional plasmid DNA (pDNA) encoding lincRNA-POU3F3 or MicroRNA-449a, and then, transfected it to VSMCs. Moreover, lentivirus-mediated KLF4 inhibitor (KLF4 siRNA) was also used in these cells. Expression of relevant proteins, such as smooth muscle myosin heavy chain (SM-MHC), alpha smooth muscle actin (α-SMA), osteopontin (OPN), and kruppel-like factor 4 (KLF4), was examined by western blot or immunofluorescence (IF) assay. CCK-8 and wound healing assays were performed to assess the growth and migration of VSMCs. qRT-PCR was used to assess linc-POU3F3 and miR-449a levels. Luciferase reporter assay was also performed., Results: POU3F3 levels were significantly higher in ISR patients compared to controls. We observed that linc-POU3F3 promoted VSMC proliferation and migration, and induced VSMC phenotypic transformation via POU3F3/miR-449a/KLF4 signaling pathway., Conclusion: Linc-POU3F3 promotes phenotypic transformation of VSMCs via POU3F3/miR-449a/KLF4 pathway. It may provide a theoretical basis to attenuate ISR via pharmacological inhibition of this biomarker or at least serve as a predictor of diagnosis or prognosis of patients with restenosis., Competing Interests: None.

Objective: Folic acid (FA) supplementation reduces the risk of atherosclerosis and stroke. Phenotypic change from differentiated to dedifferentiated vascular smooth muscle cells (VSMCs) plays an important role in atherosclerosis development; however, the exact mechanisms remain unknown. This study aimed to assess whether FA through mammalian target of rapamycin (mTOR)/P70S6K signaling inhibits platelet derived growth factor (PDGF-BB) induced VSMC dedifferentiation., Methods: VSMCs from primary cultures were identified by morphological observation and α-smooth muscle actin (α-SM-actin, α-SMA) immunocytochemistry. Then, VSMCs were induced by PDGF-BB and treated with varying FA concentrations. Rapamycin and MHY-1485 were used to inhibit or activate the mTOR/P70S6K pathway, respectively. Next, MTT, Transwell, and wound healing assays were employed to assess proliferation and migration of VSMCs. In addition, Western blotting was used to evaluate protein levels of α-SMA, calponin, osteopontin, mTOR, p-mTOR, P70S6K and p-P70S6K in VSMCs., Results: VSMCs showed phenotypic alteration from differentiated to dedifferentiated cells in response to PDGF-BB. MTT, Transwell and wound healing assays showed that FA markedly inhibited proliferation and migration in PDGF-BB-induced VSMCs, in a time and concentration-dependent manner. FA treatment increased the expression levels of the contractile phenotype marker proteins α-SMA and calponin compared with VSMCs stimulated by PDGF-BB alone. Furthermore, FA significantly suppressed mTOR and P70S6K phosphorylation compared with PDGF-BB alone. Similar to FA, downregulation of mTOR signaling by rapamycin inhibited VSMC dedifferentiation. In contrast, upregulation of mTOR signaling by MHY-1485 reversed the FA-induced inhibition of VSMC dedifferentiation., Conclusion: Folic acid inhibits dedifferentiation of PDGF-BB-induced VSMCs by suppressing mTOR/P70S6K signaling.

Background & Objective: High plasma homocysteine (Hcy) levels are known to be associated with coronary artery disease, but the precise level associated with an increased risk is yet controversial. Whether the beneficial effects of folic acid on arterial endothelial function persist over longer periods is not known. This study was carried out to assess whether folic acid supplementation could produce improvements in Hcy levels and arterial endothelial function in the patients with unstable angina (UA) and hyperhomocysteinaemia., Methods: The plasma Hcy levels of 52 cases with UA and 30 control subjects were measured by using high-performance liquid chromatography (HPLC) with fluorescence detection, plasma folic acid and vitamin B(12) levels were also measured. The patients with hyperhomocysteinaemia were treated with 5 mg of folic acid for 8 wk, and then rechecked the plasma levels of Hcy, folic acid and vitamin B(12) at the end of 4(th) and 8(th) wk. Arterial endothelial function was measured as flow-mediated dilation of the brachial artery using high-resolution B-mode ultrasound in 22 cases with UA and hyperhomocysteinaemia before and after folic acid treatment., Results: The plasma Hcy level was significant higher in the patients with UA than in the controls (19.2 +/- 4.9 vs 10.7 +/- 5.3 micromol/l, P<0.01). The plasma levels of folic acid and vitamin B12 were significant lower in the patients with UA than in the controls. There were 22(42.3%) patients with hyperhomocysteinaemia in UA group. After 4 and 8 wk of administration of folic acid, the Hcy level reduced by 20.3 and 55.3 per cent in the UA patients with hyperhomocysteinaemia, respectively. Flow-mediated dilation also improved significantly, from 6.4 +/- 1.9 to 9.0 +/- 1.2 per cent (P<0.05) after 8 wk treatment with folic acid., Interpretation & Conclusion: Plasma Hcy level was elevated in patients with UA. Folic acid can reduce the plasma Hcy levels and improve arterial endothelial function in the UA patients with hyperhomocysteinaemia.