Hydrogen peroxide-inducible clone 5 (Hic-5) as a potential therapeutic target for vascular and other disorders.

Hydrogen peroxide-inducible clone-5 (Hic-5) is a focal adhesion scaffold protein primarily expressed in vascular and visceral smooth muscle cells. We recently generated mice lacking Hic-5, which grew with no apparent abnormality (Kim-Kaneyama J, et al. J Mol Cell Cardiol.

m-Calpain induction in vascular endothelial cells on human and mouse atheromas and its roles in VE-cadherin disorganization and atherosclerosis.

Background: Although dysfunction of VE-cadherin-mediated adherence junctions in vascular endothelial cells (ECs) is thought to be one of the initial steps of atherosclerosis, little is known regarding how VE-cadherin is disrupted during atherogenic development. This study focused on the role of calpain, an intracellular cysteine protease, in the proteolytic disorganization of VE-cadherin and subsequent progression of atherosclerosis.

Methods And Results: Increased expression of m-calpain was observed in aortic ECs in atherosclerotic lesions in humans and low-density lipoprotein receptor-deficient (ldlr(-/-)) mice.

Chronic infusion of salusin-alpha and -beta exerts opposite effects on atherosclerotic lesion development in apolipoprotein E-deficient mice.

Objective: Human salusin-alpha and -beta are two-related peptides processed from the same precursor, preprosalusin. Our previous in vitro studies have shown that human macrophage foam cell formation is stimulated by salusin-beta but suppressed by salusin-alpha. Thus we investigated the effects of salusin-alpha and -beta on atherosclerotic plaque formation in vivo in apolipoprotein E-deficient (ApoE-/-) mice.

Preventive effects of heregulin-beta1 on macrophage foam cell formation and atherosclerosis.

Rationale: Human heregulins, neuregulin-1 type I polypeptides that activate proliferation, differentiation, and survival of glial cells, neurons, and myocytes, are expressed in macrophage foam cells within human coronary atherosclerotic lesions. Macrophage foam cell formation, characterized by cholesterol ester accumulation, is modulated by scavenger receptor class A (SR-A), acyl-coenzyme A:cholesterol acyltransferase (ACAT)1, and ATP-binding cassette transporter (ABC)A1.

Objective: The present study clarified the roles of heregulins in macrophage foam cell formation and atherosclerosis.

Leptin modulates ACAT1 expression and cholesterol efflux from human macrophages.

Leptin is an adipose tissue-derived hormone implicated in atherosclerosis and macrophage foam cell formation. The current study was conducted to examine the effect of leptin on cholesteryl ester accumulation in human monocytes/macrophages. Exogenously added leptin at 5 nM during differentiation of monocytes into macrophages for 7 days accelerated acetylated LDL (acetyl-LDL)-induced cholesteryl ester accumulation by 30-50%.

Human urotensin II promotes hypertension and atherosclerotic cardiovascular diseases.

Human urotensin II (U-II), the most potent vasoconstrictor undecapeptide identified to date, and its receptor (UT) are involved in the pathogenesis of systemic and pulmonary hypertension. Here, we review recent advances in our understanding of the pathophysiology of U-II with particular reference to its role in atherosclerotic cardiovascular diseases. Single-nucleotide polymorphisms of U-II gene (S89N) are associated with onset of essential hypertension, type II diabetes mellitus, and insulin resistance in the Asian population.