Update on the Pathophysiological Activities of the Cardiac Molecule Cardiotrophin-1 in Obesity

Asrih, Mohamed; Mach, François; Quercioli, Alessandra; Dallegri, Franco; Montecucco, Fabrizio

doi:10.1155/2013/370715

Cited by 8 publications

(5 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“… 21 In addition, accordingly with the role of CT-1 as multifunctional cytokine, several authors reported its participation in the regulation of glucose and lipid metabolism. 22 – 25 …”

Section: Introductionmentioning

confidence: 99%

Plasma Cardiotrophin-1 as a Marker of Hypertension and Diabetes-Induced Target Organ Damage and Cardiovascular Risk

et al. 2015

View full text Add to dashboard Cite

The search for biomarkers of hypertension and diabetes-induced damage to multiple target organs is a priority. We analyzed the correlation between plasma cardiotrophin-1 (CT-1), a chemokine that participates in cardiovascular remodeling and organ fibrosis, and a wide range of parameters currently used to diagnose morphological and functional progressive injury in left ventricle, arteries, and kidneys of diabetic and hypertensive patients, in order to validate plasma levels of CT-1 as clinical biomarker.This is an observational study with 93 type 2-diabetic patients, 209 hypertensive patients, and 82 healthy controls in which we assessed the following parameters: plasma CT-1, basal glycaemia, systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP), left ventricular hypertrophy (LVH by electrocardiographic indexes), peripheral vascular disease (by pulse wave velocity—PWV, carotid intima-media thickness—C-IMT, and ankle-brachial index—ABI), and renal impairment (by microalbuminuria, albumin/creatinine urinary ratio, plasma creatinine concentrations, and glomerular filtration rate).Hypertensive or diabetic patients have higher plasma CT-1 than control patients. CT-1 positively correlates with basal glycaemia, SBP, DBP, PP, LVH, arterial damage (increased IMT, decreased ABI), and early renal damage (microalbuminuria, elevated albumin/creatinine ratio). CT-1 also correlates with increased 10-year cardiovascular risk. Multiple linear regression analysis confirmed that CT-1 was associated with arterial injury assessed by PWV, IMT, ABI, and cardiac damage evaluated by Cornell voltage duration product.Increases in plasma CT-1 are strongly related to the intensity of several parameters associated to target organ damage supporting further investigation of its diagnostic capacity as single biomarker of cardiovascular injury and risk and, possibly, of subclinical renal damage.

show abstract

“… 21 In addition, accordingly with the role of CT-1 as multifunctional cytokine, several authors reported its participation in the regulation of glucose and lipid metabolism. 22 – 25 …”

Section: Introductionmentioning

confidence: 99%

Plasma Cardiotrophin-1 as a Marker of Hypertension and Diabetes-Induced Target Organ Damage and Cardiovascular Risk

et al. 2015

View full text Add to dashboard Cite

show abstract

“…CT-1 reduces fatty acid synthesis and insulin receptor substrate-1 expression, and induces insulin resistance in adipocytes in vitro [55]. Exogenous CT-1 administration into mice increases energy expenditure, fatty acid oxidation, and glucose cellular uptake [56]. Chronic administration of CT-1 increases lipolysis, fatty acid oxidation, mitochondrial biogenesis, and adipocyte shrinkage [56].…”

Section: Roles Of Ct-1 In Metabolic Syndromementioning

confidence: 99%

“…Exogenous CT-1 administration into mice increases energy expenditure, fatty acid oxidation, and glucose cellular uptake [56]. Chronic administration of CT-1 increases lipolysis, fatty acid oxidation, mitochondrial biogenesis, and adipocyte shrinkage [56]. However, the relationship between the in vitro and in vivo effects of CT-1 and its plasma concentrations in human metabolic diseases remains unknown so far.…”

Section: Roles Of Ct-1 In Metabolic Syndromementioning

confidence: 99%

Emerging Roles of Cardiotrophin-1 in the Pathogenesis and Biomarker of Atherosclerosis

Watanabe

Konii

Sato

2018

View full text Add to dashboard Cite

Cardiotrophin-1 (CT-1), an interleukin-6 family cytokine, is known as an active inducer capable of cardiac hypertrophy and vascular stiffness in hypertensive heart disease. CT-1 is expressed at high levels in the heart, vascular endothelial cells (ECs), and adipocytes. CT-1 stimulates inflammatory and proatherogenic molecule expression in human monocytes and ECs, as well as monocyte-EC adhesion. CT-1 enhances oxidized low-density lipoprotein-induced foam-cell formation in human monocyte-derived macrophages. CT-1 stimulates the migration, proliferation, and colloagen-1 production in human vascular smooth muscle cells. Chronic CT-1 infusion into Apoe −/− mice accelerates the development of aortic atherosclerotic lesions. CT-1 is expressed at high levels in ECs and macrophage foam cells within atheromatous plaques in Apoe −/− mice. A blockade of CT-1 using anti-CT-1 neutralizing antibody results in the prevention of atherogenesis in Apoe −/− mice. Plasma CT-1 concentrations are elevated in patients with hypertensive heart disease, ischemic heart disease, and metabolic syndrome, and are positively associated with the severity of cardiac hypertrophy, heart failure, and atherosclerosis. Increased plasma concentration of CT-1 is a predictor of death and heart failure following acute myocardial infarction. Therefore, CT-1 serves a novel therapeutic target for atherosclerosis and related diseases. Plasma CT-1 may be a reliable biomarker for atherosclerotic cardiovascular diseases.J 2018, 1 95 have provided the first evidence that CT-1 is expressed at high levels in atherosclerotic lesions and shows proatherogenic effects [15]. Other studies have reported that plasma concentrations of CT-1 are increased in patients with coronary artery disease (CAD) [16].The present review introduces the recent accumulating evidence regarding the roles of CT-1 in the pathophysiology of atherosclerosis and the potential biomarker of cardiovascular and metabolic diseases. Structure, Expression, and Function of CT-1CT-1 is a new member of the interleukin (IL)-6 cytokine family that was originally cloned from a mouse embryoid body cDNA library based on its ability to induce hypertrophy in neonatal cardiomyocytes [17]. cDNA clones of human CT-1 were isolated by screening a heart cDNA library with a mouse CT-1 probe [17]. The DNA sequence of these clones encodes a protein of 201 amino acids that is 80% identical with the 203 amino acid residue of mouse CT-1 [18]. CT-1 has a molecular weight of 21.5 kDa. Human and mouse CT-1 lack a conventional, hydrophobic, N-terminal amino acid sequence indicative of a secretion signal [18]. The amino acid sequence of rat CT-1 is 80% and 94% identical to those of human CT-1 and mouse CT-1, respectively [19]. The coding region of CT-1 is contained on 3 exons and is located on human chromosome 16p11.1-16p11.2 [18].CT-1 is expressed in the cardiovascular system as well as the brain, thymus, lungs, kidneys, liver, intestine, testes, prostate, skeletal muscles, and adipose tissue [18][19][20][21][22][23]. In cardiov...

show abstract

“…It acquired its name from the capability to induce a hypertrophic response in neonatal cardiac myocytes [7]. It is one of the pro-in ammatory cytokines belonging to the IL-6 cytokine superfamily that has been showed to do a diversity of actions in many organs such as the heart, liver, adipose tissue, and atherosclerotic arteries [8]. Growing evidence showed increased circulating CT-1 levels in humans with obesity [9] and type 2 diabetes [10], advocating that CT-1 may play a pathophysiological role in obesityrelated complications.…”

Section: Introductionmentioning

confidence: 99%

N-acetyl Cysteine Can Blunt Metabolic and Cardiovascular Effects via Down-regulation of Cardiotrophin-1 in Rat Model of Fructose-induced Metabolic Syndrome

Abdelhaffez

El-Aziz

Tohamy

et al. 2020

Preprint

View full text Add to dashboard Cite

Background Chronic fructose consumption is associated with development of obesity, insulin resistance (IR) and metabolic syndrome (MS). Cardiovascular diseases are linked to metabolic deregulation observed in MS. N-acetylcysteine (NAC) is a sulfur containing compound of Allium plants (such as garlic and onion) that increases intracellular reduced glutathione concentrations, which is an endogenous antioxidant. Methods This study investigated the ability of N-acetyl cysteine (NAC) to alleviate the metabolic disorders in fructose-induced MS in male Wistar rats and to examine its protective effect on aortic and cardiac tissues via its influence on cardiotrophin-1 (CT-1) expression. NAC (20 mg/kg b.w./day) was administered to fructose (20% w/v) induced MS animals for twelve weeks. Results Chronic fructose consumption increased body weight gain, relative heart weight, systolic blood pressure (SBP), diastolic blood pressure (DBP), IR and associated with metabolic alterations. Histological and immunohistochemical examination revealed aortic stiffness and myocardial degeneration and fibrosis together with increased CT-1 expression. Treatment with NAC improved IR, SBP, DBP and mitigated atherogenic dyslipidaemia and oxidative stress (OS). Additionally, NAC down-regulated CT-1 expression in the heart and aorta. Furthermore, CT-1 expression in the heart and aorta was positively correlated with basal glycemia, final SBP and DBP, total cholesterol, triglycerides, low density lipoproteins and negatively correlated with high density lipoproteins levels. Conclusion The findings reported here demonstrated, for the first time, the protective effect of NAC against aortic and myocardial degeneration and fibrosis through down-regulation of CT-1 in fructose induced MS animal model. Also, our results revealed the infallible role of NAC to blunt the cardiometabolic deregulation observed in MS.

show abstract

Update on the Pathophysiological Activities of the Cardiac Molecule Cardiotrophin-1 in Obesity

Cited by 8 publications

References 61 publications

Plasma Cardiotrophin-1 as a Marker of Hypertension and Diabetes-Induced Target Organ Damage and Cardiovascular Risk

Plasma Cardiotrophin-1 as a Marker of Hypertension and Diabetes-Induced Target Organ Damage and Cardiovascular Risk

Emerging Roles of Cardiotrophin-1 in the Pathogenesis and Biomarker of Atherosclerosis

N-acetyl Cysteine Can Blunt Metabolic and Cardiovascular Effects via Down-regulation of Cardiotrophin-1 in Rat Model of Fructose-induced Metabolic Syndrome

Contact Info

Product

Resources

About