Cardiac fibroblasts play a key role in the process of myocardial remodeling and myocardial fibrosis, which will eventually lead to heart failure. Quercetin Dihydrate has been studied in cardiovascular disease, but its effect on myocardial fibrosis is not clear. Here, cardiac remodeling was induced by infusion of Ang II (1000 ng/kg/min) for 2 weeks in mice. Quercetin Dihydrate was injected intraperitoneally for 25 mM/kg body weight (BW) once two days. We found that Quercetin Dihydrate significantly reduced cardiac contractile function, fibrosis, inflammation and myocardial hypertrophy induced by Ang II. Quercetin Dihydrate could inhibit the expression of Collagen I and Collagen III, which are the markers of fibroblast differentiation. We also verified the inhibitory effect of Quercetin Dihydrate on the proliferation and differentiation of fibroblasts induced by angiotensin II in vitro. Our results show that quercetin dihydrate plays a key role in the progression of myocardial fibrosis and suggests that Quercetin Dihydrate may be a promising drug for the treatment of myocardial fibrosis.

Cardiac hypertrophy are the major health challenges in the whole world. Ginsenoside Rd is an important component of cell growth and tumorigenesis, but the role and mechanism of ginsenoside Rd in pressure overload induced cardiac dysfunction and remodeling are still not fully illuminated. Here, cardiac hypertrophic remodeling and dysfunction were induced by pressure overload in mice. Myocardial histology was detected by Masson's trichrome staining and hematoxylin-eosin staining (H&E). Western blot was used to detect protein levels of signal mediators. Cardiac function was evaluated by echocardiography, and qPCR analysis was used to detect mRNA expression of hypertrophy and fibrosis markers. Cardiomyocyte size was detected by Wheat germ agglutinin (WGA) staining. Dihydroethidine (DHE) staining was used to detect oxidative stress. We also detected the influence of Ginsenoside Rd on rat neonatal cardiac myocytes (NRCMs) treated by Phenylephrine (PE). Our results showed that Ginsenoside Rd significantly improved pressure overload induced contractile dysfunction, fibrosis, cardiac hypertrophy, inflammation and oxidative stress in mice. Moreover, protein levels of AKT, calcineurin A, ERK1/2 and TGF-β1 were significantly decreased in the Ginsenoside Rd-treated hearts as compared to control. Ginsenoside Rd treated in cardiomyocytes inhibited PE-induced cardiomyocyte hypertrophy. These results revealed that ginsenoside Rd improved cardiac dysfunction and remodeling induced by pressure overload, which is related to the inhibition of a variety of signaling pathways.

Uric acid is an effective antioxidant. Oxidized low-density lipoprotein (ox-LDL) is derived from circulating LDL and promotes atherosclerosis. The Keap1-Nrf2-ARE pathway is a key body pathway involved in protection against internal and external oxidative damages. The role of uric acid on vascular endothelial function damaged by ox-LDL, and its effect on the Keap1-Nrf2-ARE pathway has not been fully explored. HUVECs were treated with different concentrations of uric acid and ox-LDL to explore the effect of uric acid in vitro. Cell phenotype was determined by cytometry and Western blot. Nuclear translocation of Nrf2 was determined by immunofluorescence. Coimmunoprecipitation was used to determine the level of Nrf2 ubiquitination. A microfluidic device was used to mimic the vascular environment in the body, and the level of mRNA levels of inflammatory factors was determined by RT-PCR. The findings of this study show that suitable uric acid can significantly reduce endothelial damage caused by ox-LDL, such as oxidative stress, inflammation, and increased adhesion. In addition, uric acid reduced Nrf2 ubiquitination and increased nuclear translocation of Nrf2 protein, thus activating the Keap1-Nrf2-ARE pathway and playing a protective role. Interestingly, the effects of UA were significantly inhibited by administration of Brusatol, an inhibitor of Nrf2. In summary, suitable concentrations of uric acid can alleviate the oxidative stress level of endothelial cells through Nrf2 nuclear translocation and further protect cells from damage.

The cardiovascular disease pathogenesis is extremely complex and seriously threatens human health. Cardiomyocyte death plays a significant role in cardiovascular disease occurrence and development. In addition to the previously revealed modes of cell death (apoptosis, autophagy, and pyroptosis), ferroptosis is highly related to the development of cardiovascular diseases, including arrhythmia, atherosclerosis, and myocardial ischemia/reperfusion. Ferroptosis is a novel cell death pathway driven by lipid peroxidation and iron overload. Lipid, amino acid, and iron metabolism regulate the ferroptosis pathway. Small molecule compounds (iron chelators, antioxidants, and ferroptosis inhibitors) and genetic programming can alleviate or prevent cardiovascular disease by inhibiting the ferroptosis pathway. Ferroptosis plays a key role in various cardiovascular disease occurrence and development, and inhibiting ferroptosis in cardiomyocytes is expected to become a feasible treatment method. In this mini-review, we systematically summarize the molecular mechanisms of ferroptosis in different cardiovascular diseases, delineate the regulatory network between ferroptosis and cardiovascular diseases, and highlight its potential therapeutic targets.

The heart undergoes pathological cardiac hypertrophy as an adaptive response to prolonged pathological stimulation, leading to cardiomyocyte hypertrophy, fibroblast proliferation, and an increase in extracellular matrix. Chinese medicine monomers are now receiving much attention for the treatment of cardiac hypertrophy and myocardial remodeling. Biochanin A (BCA) is a kind of flavonoid structural monomer, which has a certain therapeutic effect on bone thinning disease, aging syndrome, lung cancer, etc. Moreover, it exhibits hypoglycemic, anti-inflammatory, anti-oxidation, anti-bacteria and other pharmacological properties. It is still unknown whether BCA has an impact on the mechanism of TAC-induced cardiac hypertrophy. Here, cardiac remodeling was induced by TAC. BCA was injected intraperitoneally at 25 and 50 mg/kg/day one week in advance. Masson, WGA, DHE and other pathological staining and serum were used to detect the inhibitory effect of BCA on cardiac hypertrophy in mice. The anti-hypertrophic effect of BCA was demonstrated by studying the pathological manifestations of Neonatal rat cardiomyocytes (NRCMs) and cardiac fibroblasts (CFs) in vitro. The results showed that BCA significantly reduced TAC-induced fibrosis, inflammation, oxidative stress, and myocardial hypertrophy. BCA inhibited Ang II-induced cell hypertrophy and oxidative stress in NRCMs in vitro and Ang II-induced CF migration, proliferation, and collagen secretion. This suggests that BCA plays a key role in inhibiting the progression of myocardial remodeling, suggesting that BCA may be a promising agent for the treatment of myocardial hypertrophy and fibrosis.

Background . Ubiquitin‐like modifier activating enzyme 1 (UBA1) is the first and major E1 activating enzyme in ubiquitin activation, the initial step of the ubiquitin‐proteasome system. Defects in the expression or activity of UBA1 correlate with several neurodegenerative and cardiovascular disorders. However, whether UBA1 contributes to atherosclerosis is not defined. Methods and Results . Atherosclerosis was induced in apolipoprotein E‐knockout ( Apoe-/- ) mice fed on an atherogenic diet. UBA1 expression, detected by immunohistochemical staining, was found to be significantly increased in the atherosclerotic plaques, which confirmed to be mainly derived from lesional CD68 ⁺ macrophages via immunofluorescence costaining. Inactivation of UBA1 by the specific inhibitor PYR‐41 did not alter the main metabolic parameters during atherogenic diet feeding but suppressed atherosclerosis development with less macrophage infiltration and plaque necrosis. PYR‐41 did not alter circulating immune cells determined by flow cytometry but significantly reduced aortic mRNA levels of cytokines related to monocyte recruitment ( Mcp-1 , Vcam-1 , and Icam-1 ) and macrophage proinflammatory responses ( Il-1β and Il-6 ). Besides, PYR‐41 also suppressed aortic mRNA expression of NADPH oxidase ( Nox1 , Nox2 , and Nox4 ) and lesional oxidative stress levels, determined by DHE staining. In vitro , PYR‐41 blunted ox‐LDL‐induced lipid deposition and expression of proinflammatory cytokines ( Il-1β and Il-6 ) and NADPH oxidases ( Nox1 , Nox2 , and Nox4 ) in cultured RAW264.7 macrophages. Conclusions . We demonstrated that UBA1 expression was upregulated and mainly derived from macrophages in the atherosclerotic plaques and inactivation of UBA1 by PYR‐41 suppressed atherosclerosis development probably through inhibiting macrophage proinflammatory response and oxidative stress. Our data suggested that UBA1 might be explored as a potential pharmaceutical target against atherosclerosis.