C1q/TNF‐related protein‐1 functions to protect against acute ischemic injury in the heart

Abstract

Obesity is associated with an increased risk of cardiovascular disease. C1q/TNF-related protein (CTRP)-1 is a poorly characterized adipokine that is up-regulated in association with ischemic heart disease. We investigated the role of CTRP1 in myocardial ischemia injury. CTRP1-knockout mice showed increased myocardial infarct size, cardiomyocyte apoptosis, and proinflammatory gene expression after I/R compared with wild-type (WT) mice. In contrast, systemic delivery of CTRP1 attenuated myocardial damage after I/R in WT mice. Treatment of cardiomyocytes with CTRP1 led to reduction of hypoxia-reoxygenation-induced apoptosis and lipopolysaccharide-stimulated expression of proinflammatory cytokines, which was reversed by inhibition of sphingosine-1-phosphate (S1P) signaling. Treatment of cardiomyocytes with CTRP1 also resulted in the increased production of cAMP, which was blocked by suppression of S1P signaling. The antiapoptotic and anti-inflammatory actions of CTRP1 were cancelled by inhibition of adenylyl cyclase or knockdown of adiponectin receptor 1. Furthermore, blockade of S1P signaling reversed CTRP1-mediated inhibition of myocardial infarct size, apoptosis, and inflammation after I/R in vivo. These data indicate that CTRP1 protects against myocardial ischemic injury by reducing apoptosis and inflammatory response through activation of the S1P/cAMP signaling pathways in cardiomyocytes, suggesting that CTRP1 plays a crucial role in the pathogenesis of ischemic heart disease.

Association Between C1q/TNF-Related Protein-1 Levels in Human Plasma and Epicardial Adipose Tissues and Congestive Heart Failure

“…Some previous reports have suggested that the CTRP1 levels were increased in patients with stable coronary heart disease and mice with acute ischaemic injury [20, 21]. In this study, we excluded patients with acute myocardial infarction and found dynamic changes in the plasma concentration of CTRP1 in CHF patients.…”

C1q/TNF‐Related Protein 3 (CTRP3) Function and Regulation

“…In 2004, Wong et al characterized a novel family of adipose tissue-derived cytokines, collectively called adipokines, referred to as Complement C 1q T umor necrosis factor- R elated P roteins (CTRPs) (76), like adiponectin and tumor necrosis factor (TNF) these CTRPs all contain a C1q globular domain and are characterized together as the C1q/TNF superfamily (62). To date, this superfamily has been documented to have a wide range and opposing effects on metabolism, food intake, inflammation, tumor metastasis, apoptosis, vascular disorders, ischemic injury, and even sexual reproduction (7, 8, 25, 29, 30, 49, 51, 57, 62, 64, 68, 69, 74-76, 81, 84, 89). The purpose of this review is to carefully summarize the research that has been accomplished on one of these proteins, CTRP3.…”

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

“…(21,22) Although there is evidence on the protective role of CTRP1 in murine heart injuries, the exact role of CTRP1 in these conditions is still not fully understood and requires further studies. (23) CTRP5, another member of CTRPs family also expressed in a wide range of tissues including adipose tissue, eye, testis, skeletal muscle, brain, spleen, uterus, and ciliary epithelium but like CTRP1, adipose tissue is considered as the main secretor. (21) CTRP5 increases glucose uptake via stimulating plasma membrane incorporation of the glucose transporter 4 (GLUT4) into plasma membrane by a mechanism dependent on AMPK phosphorylation.…”