Search

Atherosclerosis (AS) is characterized by lipids metabolism disorder and inflammatory response. Accumulating evidence has demonstrated that Wingless type 5a (Wnt5a) is implicated in cardiovascular diseases through non-canonical Wnt cascades. However, its precise role during the pathogenesis of AS is still unclear. Therefore, the present study aims to investigate the role and the underlying mechanism of Wnt5a/receptor tyrosine kinase-like orphan receptor 2 (Ror2) pathways in the promotion of AS process through affecting lipid accumulation and inflammation. In atherosclerotic clinical samples, Wnt5a levels were measured by using enzyme-linked immunosorbent assay (ELISA) assay. In vivo experiments were conducted by using apolipoprotein E knockout (apoE−/−) mice model. Vascular smooth muscle cells (VSMCs) were applied for in vitro studies. Wnt5a was highly expressed in both of atherosclerotic clinical samples and apoE−/− mice. The knockdown of Wnt5a significantly inhibited cholesterol accumulation and inflammatory response. Additionally, the lipopolysaccharide (LPS)-induced inflammation aggravated the cholesterol accumulation and decreased adenosine triphosphate (ATP)-binding cassette transporter A1 (ABCA1) expression in VSMCs. Depletion of intracellular cholesterol by β-cyclodextrin (β-CD) led to the upregulation of ABCA1 and the inhibition of inflammation. Conversely, the overexpression of Wnt5a inhibited ABCA1 expression, facilitated cholesterol accumulation, impared cholesterol efflux, promoted NF-κB nuclear translocation and the inflammatory cytokines secretion. Moreover, the knockdown of Ror2 increased ABCA1 expression and reduced Wnt5a-induced cholesterol accumulation and inflammatory responses. Furthermore, the knockdown of ABCA1 enhanced cholesterol accumulation and inflammatory response. Therefore, Wnt5a/Ror2 pathway was critical in regulating cholesterol homeostasis and inflammatory response, which might be a promising therapeutic target for AS therapy. Unlabelled Image • A close correlation between the cholesterol disorder and inflammatory response. • Wnt5a/Ror2 pathway is critical in cholesterol homeostasis and inflammatory response. • ABCA1 involved in Wnt5a/Ror2 axis-mediated cholesterol homeostasis and inflammation. [ABSTRACT FROM AUTHOR]

Vascular remodelling refers to abnormal changes in the structure and function of blood vessel walls caused by injury, and is the main pathological basis of cardiovascular diseases such as atherosclerosis, hypertension, and pulmonary hypertension. Among them, the neointimal hyperplasia caused by abnormal proliferation of vascular smooth muscle cells (VSMCs) plays a key role in the pathogenesis of vascular remodelling. Perivascular adipose tissue (PVAT) can release vasoactive substances to target VSMCs and regulate the pathological process of vascular remodelling. Specifically, PVAT can promote the conversion of VSMCs phenotype from contraction to synthesis by secreting visfatin, leptin, and resistin, and participate in the development of vascular remodelling-related diseases. Conversely, it can also inhibit the growth of VSMCs by secreting adiponectin and omentin to prevent neointimal hyperplasia and alleviate vascular remodelling. Therefore, exploring and developing new drugs or other treatments that facilitate the beneficial effects of PVAT on VSMCs is a potential strategy for prevention or treatment of vascular remodelling-related cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Vascular smooth muscle cells (VSMCs) is one of the main intracellular components of the blood vessel wall. The abnormalities of VSMCs participate in the development of cardiovascular diseases such as atherosclerosis, hypertension, and restenosis, especially the formation and stability of atherosclerotic plaques. Autophagy is involved in the regulation of proliferation, migration and phenotype switching of VSMCs, which in turn affects the pathological process of atherosclerosis. However, the autophagy of VSMCs has a dual effect on cells survival. Autophagy is induced in VSMCs by various stimuli such as 7-ketocholesterol (7-KC), unsaturated lipid peroxidation-derived aldehyde and excess free cholesterol, thereby promoting VSMCs survival and stabilising atherosclerotic plaque. Conversely, autophagy caused by factors such as osteopontin (OPN), angiotensin II (Ang II) and nicotine can accelerate the death of VSMCs, further accelerating atherosclerotic lesions. In addition, mitophagy and lipophagy as selective autophagy are also involved in the outcome of VSMCs as well as progression of atherosclerotic lesion. Currently, there are only a few drugs available to induce VSMCs autophagy, such as atorvastatin, telmisartan and so on. Due to the important role of VSMCs autophagy in the progression of atherosclerosis plaques, drugs that directly target autophagy of VSMCs are urgently needed to be developed. [ABSTRACT FROM AUTHOR]

Abstract Long noncoding RNA-steroid receptor RNA activator (LncRNA-SRA) is transcribed from a class of noncoding genes, and plays a critical role in regulating cell proliferation. However, the effect of lncRNA-SRA remains unclear in vascular proliferative diseases. In the present study, we overexpressed lncRNA-SRA in vitro , then investigated the biological consequences. A vascular damage mice model was constructed by performing femoral artery wire injury. LncRNA-SRA was overexpressed in the injured arteries, and significantly promoted the expression of ki67, thereby caused an overall increase in neointima formation. LncRNA-SRA overexpression led to the proliferation and migration of vascular smooth muscle cells (VSMCs). By stimulating the phosphorylation of MEK, ERK and CREB (cyclic nucleotide responsive element binding protein), lncRNA-SRA promoted VSMC proliferation. Meanwhile, these effects were blocked by the MEK inhibitor U0126. Therefore, lncRNA-SRA promoted VSMC proliferation by activating the MEK-ERK-CREB pathway. LncRNA-SRA could be a promising therapeutic target in vascular diseases characterized by neointimal hyperplasia. Graphical abstract Unlabelled Image [ABSTRACT FROM AUTHOR]