Abstract
The aims of this study were to check whether different biomarkers of inflammatory, apoptotic, immunological or lipid pathways had altered their expression in the occluded popliteal artery (OPA) compared with the internal mammary artery (IMA) and femoral vein (FV) and to examine whether glycemic control influenced the expression of these genes. The study included 20 patients with advanced atherosclerosis and type 2 diabetes mellitus, 15 of whom had peripheral arterial occlusive disease (PAOD), from whom samples of OPA and FV were collected. PAOD patients were classified based on their HbA1c as well (HbA1c ≤ 6.5) or poorly (HbA1c > 6.5) controlled patients. Controls for arteries without atherosclerosis comprised 5 IMA from patients with ischemic cardiomyopathy (ICM). mRNA, protein expression and histological studies were analyzed in IMA, OPA and FV. After analyzing 46 genes, OPA showed higher expression levels than IMA or FV for genes involved in thrombosis (F3), apoptosis (MMP2, MMP9, TIMP1 and TIM3), lipid metabolism (LRP1 and NDUFA), immune response (TLR2) and monocytes adhesion (CD83). Remarkably, MMP-9 expression was lower in OPA from well-controlled patients. In FV from diabetic patients with HbA1c ≤6.5, gene expression levels of BCL2, CDKN1A, COX2, NDUFA and SREBP2 were higher than in FV from those with HbA1c >6.5.The atherosclerotic process in OPA from diabetic patients was associated with high expression levels of inflammatory, lipid metabolism and apoptotic biomarkers. The degree of glycemic control was associated with gene expression markers of apoptosis, lipid metabolism and antioxidants in FV. However, the effect of glycemic control on pro-atherosclerotic gene expression was very low in arteries with established atherosclerosis.
Highlights
Cardiovascular diseases (CVD) are highly prevalent in the general population, affecting most adults over 60 years of age
Control arteries with no atherosclerosis consisted of internal mammary artery (IMA) biopsies collected from 5 diabetic patients with good glycemic control and severe ischemia due to ischemic cardiomyopathy (ICM) who were undergoing coronary revascularization
The IMA showed a normal histology with the adventitia composed of connective tissue as well as collagen and elastic fibers, the media layer composed of smooth muscle and elastic fibers, and the intima layer, the inner layer, composed of an elastic membrane lining and smooth endothelium covered by elastic tissues (Figure 1A)
Summary
Cardiovascular diseases (CVD) are highly prevalent in the general population, affecting most adults over 60 years of age. Vascular endothelium has unique responses to hemodynamic forces. The flow and hemodynamic forces are not uniform in the vascular system. The endothelium of the vascular circulation is exposed to hemodynamic forces of greater magnitude. The pathophysiology of arterial thrombosis is different from that of venous thrombosis. In the arteries there is altered endothelium-platelet adhesion, greatly influenced by hemodynamic forces, while the major factors for venous thrombosis are the phenomena of slow or stagnant blood flow, combined with hypercoagulability situations [2]. A disturbed flow leads to inflammation and venous thrombosis, and the development of chronic vessel disease, such as peripheral arterial disease
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
