Role of cardiotrophin-1 in cardiovascular regulation
Cardiotrophin-1 (CT-1) is a transmembrane signaling glycoprotein (gp)130 ligand, a leukemia inhibitory factor (LIF) receptor and a heart-targeting cytokine. CT-1 is a new member of the interleukin IL-6 type cytokine family and has potent hypertrophic and survival effects on cardiac myocytes [1]. Several factors could stimulate cardiac CT-1 expression such as hypoxia, reactive oxygen species, angiotensin II, aldosterone, urocortin, glucose and insulin, and fibroblast growth factor-2. CT-1 mediates its hypertrophic and cytoprotective properties through the Janus kinase/signal transducers and activators of transcription (JAK/STAT), mitogen-activated protein (MAP) kinase, phosphatidylinositol (PI-3) kinase, and nuclear factor kappa B (NFκB) pathways [2]. CT-1 was originally identified in cardiomyocytes (heart) but CT-1 gene (located on chromosome 16p11.1–16p11.2) and protein (that encodes 201 amino acids) expression also occurs in the liver, lung, kidney, skeletal muscle and adipose tissues (adipocytes is an important cellular source of CT-1).
Plasma cardiotrophin-1 (CT-1) levels are elevated in cardiovascular diseases (CVDs) such as hypertension, valve diseases, congestive heart failure, coronary artery diseases, metabolic syndrome, and chronic kidney diseases. Circulating levels of CT-1 increase with the severity of the CVDs [3]. CT-1 exerts a protective function in the adult heart by inducing cell hypertrophy (enlargement). Recent research says that CT-1 specifically protects the cardiac myocytes from ischaemic damage when given prior to the ischaemia and at the time of reoxygenation. CT-1 induces the pathological hypertrophic response and could be therapeutically used in the treatment of ischaemic damage in the heart [4].
Recent evidence suggests that CT-1 acts as a biomarker for LVH (left ventricular hypertrophy) and impaired cardiac function in patients with hypertension. Recent study, by a team of researchers from The Ottawa Hospital, the University of Ottawa, the University of Ottawa Heart Institute and Carleton University discovered that CT-1 protein could be used as an “exercise pill” that can trick the heart into repairing damage and improving blood flow. This “pill” i.e. CT-1 protein could help improve the function of a failing heart and boost blood flow by mimicking the effects of a visit to the gym that could revolutionize the lives of hundreds of thousands of heart disease sufferers [5].
Also local and systemic concentrations of CT-1 plays a critical role in obesity. A recent study showed that acute and chronic treatments with recombinant CT-1 were able to correct insulin resistance in animal models of genetic and acquired obesity. A recent study also found that cardiotrophin-1 induces Matrix Metalloproteinase-1 (MMP) in human aortic endothelial cells (HAECs) [6]. Recent research suggests that CT-1 induces the proteolytic potential in HAECs by upregulating MMP-1 expression through ERK1/2, p38 MAP kinase, JNK and JAK/STAT pathways, and also suggests that CT-1 may play an important role in the pathophysiology of atherosclerosis and plaque instability. All data shows that CT-1 has a huge impact on cardiovascular regulation and heart disease protection.
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