Alterations of specific biomarkers of metabolic pathways in vascular tree from patients with Type 2 diabetes

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.

Circulating soluble low-density lipoprotein receptor-related protein 1 (sLRP1) concentration is associated with hypercholesterolemia: A new potential biomarker for atherosclerosis

“…In in vitro experiments, we have explored whether atherogenic lipoproteins promote the release of sLRP1 from hVSMC and HMDM. As expected [31], native LDL (nLDL) and agLDL increased intracellular CE levels at each time (8,16 and 32 h) in hVSMC (Fig. 3A, B).…”

“…In a model of angiotensin II-infused rats, we found a significant and positive correlation between LRP1 mRNA expression and systolic blood pressure in both thoracic and abdominal aortas [15]. Finally, in type 2 diabetic patients with clinical stage IV of peripheral arterial occlusive disease, we reported the overexpression of LRP1 in occluded popliteal artery with atherosclerotic plaque compared to femoral veins [16].…”

Circulating T Cells Exhibit Different TIM3/Galectin-9 Expression in Patients with Obesity and Obesity-Related Diabetes

“…Once the patients had developed diabetes, TIM3 became dysfunctional and downregulated. The lower expression of TIM3 may also lose the inhibitory ability to CD4 + T cells, which are involved in the pathogenesis of T2DM [ 25 , 26 ].…”

MicroRNA profiling of diabetic atherosclerosis in a rat model

“…KEGG pathway enrichment analysis identified several glucose and lipid metabolism related pathways associated with DA including “metabolic pathways”, “Type II diabetes mellitus”, “insulin signaling pathway”, and “insulin secretion” that are consistent with altered metabolic status of diabetic animals, supporting the relevance of the study approach. In DM patients, “metabolic pathways” and “type II diabetes mellitus” pathway signaling increase the risk of developing DA [ 29 , 30 ]. Additionally, the insulin related pathway findings are consistent with the major role of insulin signaling in modulating the pathogenesis of both type 2 diabetes and AS [ 31 , 32 ].…”