Abstract
BackgroundSterol regulatory-element binding proteins (SREBPs) and mir-33 (miR-33a, miR-33b), which are encoded by the introns of SREBPs, are key factors in the lipid metabolism pathway. SREBPs mRNA in circulating leucocyte and carotid plaques, along with various risk factors that associated with Coronary Atherosclerotic Disease (CAD) were investigated in a central Chinese cohort.MethodsA total of 218 coronary atherosclerotic disease (CAD) patients, and 178 non-CAD controls, were recruited to collect leukocytes. Carotid plaques and peripheral blood were obtained from CAD patients undergoing carotid endarterectomy (CEA) (n = 12) while THP-1 and peripheral blood mononuclear cells (PBMCs) were stimulated with Oxidized low-density lipoprotein (ox-LDL) to establish an in vitro foam cell formation model. SREBPs and miR-33 levels were quantified by qPCR. Routine biochemical markers were measured using standard procedures.ResultsSREBP-1 mRNA level of circulating leucocytes in CAD patients were significantly lower than in non-CAD controls (p = 0.005). After stratification coronary artery atherosclerotic complexity, we detected a significant reduction of SREBP-1 in high-risk complexity CAD patients (SYNTAX score > 23) (p = 0.001). Logistic regression analysis indicated that decreased expression of SREBP-1 was a risk factor of CAD (odds ratio (OR) =0.48, 95% confidence interval (CI) = 0.30~0.76, p = 0.002) after adjusting clinical confounders; the mRNA levels of SREBPs in carotid plaques correlated with the corresponding value in circulating leukocytes (SREBP-1 r = 0.717, p = 0.010; SREBP-2 r = 0.612, p = 0.034). Finally, there was no significant difference in serum miR-33 levels between CAD patients and controls.ConclusionsOur finding suggesting a potential role in the adjustment of established CAD risk. The future clarification of how SREBP-1 influence the pathogenesis of CAD might pave the way for the development of novel therapeutic methods.
Highlights
Sterol regulatory-element binding proteins (SREBPs) and mir-33, which are encoded by the introns of Sterol regulatory element binding proteins (SREBP), are key factors in the lipid metabolism pathway
There were no statistically significant differences observed in terms of age, gender, Lactate dehydrogenase (LDH), Cystatin C (CysC) or Glycated serum protein (GSP) when compared between the control and Coronary Atherosclerotic Disease (CAD) groups (p = 0.214, 0.120, 0.272, 0.445, 0.086, respectively)
Expressed SREBP Message ribonucleic acid (mRNA) in CAD patients Compared with the control group, the CAD group had significantly lower levels of SREBP-1 mRNA; overall, these levels showed a reduction of approximately 35%
Summary
Sterol regulatory-element binding proteins (SREBPs) and mir-33 (miR-33a, miR-33b), which are encoded by the introns of SREBPs, are key factors in the lipid metabolism pathway. SREBP-1 activates the synthesis of fatty acids and triglycerides while SREBP-2 increases the synthesis of cholesterol [2]. All SREBPs are synthesized as transcriptionally inactive precursors that are bound to the endoplasmic reticulum (ER) and the nuclear envelope. Their transcriptional activation requires binding to SREBP cleavage-activating protein (SCAP); binding translocate their inactive precursors form the ER to the Golgi and subsequent migration into nucleus, where they can bind to sterol response elements (SREs) in the promoter region of target genes and thereby modulate gene transcription [4]. Activation of SREBP transcription leads to the increased expression of microRNAs-33, miR-33a and miR-33b, which are located within intron of SREBP-2 and intron of SREBP-1, respectively [5]. The co-expression of the two miR-33 forms, along with their host genes, can function in a synergistic manner to further facilitate a return to homeostasis [6]
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