Association of C1q/TNF-Related Protein-3 (CTRP3) and CTRP13 Serum Levels with Coronary Artery Disease in Subjects with and without Type 2 Diabetes Mellitus

Abstract

C1q/TNF-Related Protein-3 (CTRP3) and CTRP13 are two newly discovered adipokines regulating glucose and lipid metabolism. But their role in type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD) is still in infancy. The aim of this study was to investigate the associations of gene expression and serum levels of CTRP3 and CTRP13 with CAD, metabolic and inflammatory markers in patients with and without T2DM. Serum levels of CTRP3, CTRP13, adiponectin and inflammatory cytokines and their gene expression in peripheral blood mononuclear cells (PBMCs) were determined in 172 subjects categorized as group I (without T2DM and CAD), group II (with CAD but no T2DM), group III (with T2DM but no CAD) and group IV (with T2DM and CAD). Serum levels and gene expression of CTRP3, CTRP13 and adiponectin in the group I were higher compared to other groups. Inflammatory cytokines in the control group were lower than other groups too. CTRP3 serum levels have an independent association with BMI, smoking and CTRP3 gene expression; also CTRP13 serum levels has an independent association with BMI, HDL-C, insulin, HOMA-IR, HbA1c and TNF-α. Decreased serum levels of CTRP3 and CTRP13 were also associated with CAD. It appears that the decreased levels of CTRP3 and especially CTRP13 were associated with increased risk of T2DM and CAD. These findings suggest an emerging role of these adipokines in the pathogenesis of CAD, but further studies are necessary to establish this concept.

Circulating levels of C1q/TNF‐α‐related protein 6 (CTRP6) in polycystic ovary syndrome

“…CTRP3, also known as cartonectin, regulates glucose homeostasis and exhibits anti‐inflammatory immunomodulatory role . Low circulating levels of CTRP3 have been correlated with insulin resistance, T2DM, gestational diabetes mellitus, NAFLD, and coronary artery disease (CAD) . Similar to adiponectin, CTRP5 stimulates glucose uptake and fatty acid oxidation in myocytes and adipocytes, and is considered as a counter‐regulator of CTRP3 .…”

Adipose tissue-derived cytokines, CTRPs as biomarkers and therapeutic targets in metabolism and the cardiovascular system

“…Novel metabolic/immune regulator; modulating both inflammation and insulin sensitivity; regulates fat development; alleviates AngII-induced hypertension and vascular endothelial dysfunction; potential therapeutic target for the prevention of skin fibrosis; endogenous complement regulator [5,29,68,69] 7 Adipose tissue, lung Improves insulin sensitivity; beneficial metabolic outcomes in the setting of obesity and diabetes [9,54] 8 (8B) Lung, testis, absent in mice Blocks glioblastoma dissemination within the brain [14,70] 9 (9A,9B) Cardiac tissue, adipose tissue Important in the development of type 2 diabetes; novel metabolic regulator and a new component of the metabolic network that links adipose tissue to lipid metabolism in skeletal muscle and liver; prevents vascular restenosis after angioplasty, hepatic steatosis and hypertension; stabilizes plaque, improves endothelial cell survival and function [12,20,48,[71][72][73] 10 Eye, adipose tissue Regulates metabolism, adipose tissue homeostasis [3,23] 11 Adipose tissue New regulator of adipogenesis; maintains adipose tissue homeostasis [3,74] 12 Adipose tissue Novel biomarkers for the prediction and early diagnosis of T2DM; regulates glucose and lipid metabolism and whole-body glucose homeostasis [24,50,51,75,76] 13 Adipose tissue, brain Associated with increased risk of T2DM and coronary artery disease and non-alcoholic fatty liver disease; negative association with metabolism; modulates whole-body energy balance [2,24,27,77,78] 14 Brain, adipose tissue Promotes tissue regeneration, and recovery of ischemic heart disease; maintains adipose tissue homeostasis by generating complexes with CTRP11 [74] 15 Skeletal muscle Modulates energy homeostasis and metabolic circuit; modulates inter-tissue crosstalk [21,79] ISR: in-stent restenosis; PCI: percutaneous coronary intervention; DES: d...…”

“…The measurement of circulating CTRPs in serum is through commercially available ELISA kits provide by Aviscera company (Santa Clara, USA). CTRP3, in recent human studies, was increased in subjects with the cardio-metabolic syndrome and is associated with various cardiometabolic risk factors including the triglycerides, highdensity lipoprotein-cholesterol, waist-to-hip ratio, and eGFR, which indicate the decreased CTRP3 levels that may serve as a predictor of coronary artery disease, while CTRP13 cannot serve as a predictor candidate since there is evidence that CTRP13 mRNA expression is increased in the setting of obesity [26,27] . This contradiction may be attributed to different nature of human and rodent studies.…”

The circulating levels of CTRP5 and the ratio of CTRP1 to CTRP5 plasma levels are significant predictors for cIMT value in patients with type 2 diabetes

“…(14,15) The alteration in circulating levels of CTRPs has been reported in various metabolic diseases such as T2D, obesity, CVD, fatty liver disease and metabolic syndrome. (16)(17)(18)(19) CTRP1 is expressed in various tissues including adipose tissue, liver, muscles, kidneys, and heart. (14) Muscles are primary targets for CTRP1 as it activates AMPK and MAPK signaling pathways and promotes glucose uptake, ameliorates insulin resistance and increases fat oxidation.…”