Expression of retinoic acid target genes in coronary artery disease

Abstract

Coronary atherosclerosis can lead to myocardial infarction, and secondarily to post-infarct remodelling and heart failure. Retinoic acid (RA) influences cell proliferation. We hypothesized that RA could influence gene expression and proliferation of cardiovascular cells. Left ventricular biopsies from patients with end-stage heart failure due to coronary artery disease (CAD) or dilated cardiomyopathy were investigated for the content of RA metabolites using liquid chromatography mass spectrometry (LC-MS/MS), and compared with healthy donors. All-trans retinoic acid (ATRA) was increased in the hearts of CAD patients. Gene expression (quantitative PCR) of RA target genes was not influenced in failing hearts, but was increased in the hearts of patients with CAD undergoing open heart surgery. The expression of RA target genes was increased in atherosclerotic lesions from carotid arteries compared to healthy arteries. Stimulation of cardiomyocytes, cardiofibroblasts, smooth muscle cells and endothelial cells with ATRA increased the gene expression of the key enzymes. Cardiofibroblast and smooth muscle cell proliferation were reduced by ATRA, which increased endothelial cell proliferation. Coronary artery disease leads to increased expression of RA target genes. ATRA accumulated in the failing human heart. All investigated cell types present in the heart had induced expression of RA target genes when stimulated with ATRA, which also influenced cell proliferation.

All-trans retinoic acid effectively reduces atheroma plaque size in a rabbit model of high-fat-induced atherosclerosis

“…20 In another study by Bilbija et al, an overexpression of retinoic acid target genes was shown in coronary artery disease (CAD). 24 Bilbija et al also reported that atRA has antiproliferative effects on cardiomyocytes and cardiofibroblasts and concluded that the antiproliferative effects of atRA may be beneficial because it may be used to delay cardiomyocyte remodeling, reduce restenosis and preserve the functions of the cardiovascular system. 24 But in none of the related studies are the underlying signal transduction pathways, which lead to AS reduction and inhibition, clearly defined.…”

All‑trans retinoic acid reduces endothelin‑1 expression and increases endothelial nitric oxide synthase phosphorylation in rabbits with atherosclerosis

“…The formation mechanisms of AS are complex and numerous, and the structural and functional damage of the vascular endothelium is regarded as the initial step for the genesis of AS (21,22), which influences the AS lesion degree (23,24). It is established that under the action of numerous AS risk factors, including hyperlipidemia, hypertension, diabetes and smoking, the endothelial function is damaged and may be aggravated gradually with AS development (25).…”

Psoriasis and Cardiovascular Comorbidities: Focusing on Severe Vascular Events, Cardiovascular Risk Factors and Implications for Treatment

“…In a subset of patients, acitretin may cause hyperlipidemia, which should be actively treated to avoid increased cardiovascular risk. Previous studies in humans and animals have shown that retinoids may improve and ameliorate the formation of atherosclerotic plaques [ 255 , 256 , 257 , 258 , 259 , 260 , 261 ]. Further investigations are required to determine whether treatment of psoriasis patients with retinoids may prevent the development of atherosclerosis and decrease the risk of cardiovascular events.…”