Relationship Between Hypertension and Atherosclerosis: From a Viewpoint of the Most Potent Vasoconstrictor Human Urotensin II

Watanabe, Takuya; Kanome, Tomoko; Miyazaki, Akira

doi:10.2174/157340206778132536

Cited by 3 publications

(1 citation statement)

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“…Hypertension is regarded as a promotive and risk factor of atherosclerosis [1]. Several lines of evidence have shown that endothelial injury, an initial step of atherosclerosis, is caused by hypertension-induced pressure overload, stretch, or shear stress on the artery wall [2].…”

Section: Introductionmentioning

confidence: 99%

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

Watanabe

Konii

Sato

2018

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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...

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Section: Introductionmentioning

confidence: 99%