Novel role for retinol-binding protein 4 in the regulation of blood pressure

Abstract

Elevated levels of serum retinol-binding protein 4 (RBP4) contribute to insulin resistance and correlate with increased prevalence of hypertension and myocardial infarction. We sought to determine whether lowering RBP4 would improve blood pressure (BP) and protect against obesity-or angiotensin (Ang)-II-induced hypertension. Systolic and diastolic BP were lower in the RBP4-knockout (RBP4-KO) mice and higher in the RBP4-overexpressing (RBP4-Tg) mice compared with BP in the wild-type (WT) littermates. Carbachol-induced vasodilatation was increased in arteries from the RBP4-KO compared with the WT mice and was impaired in the RBP4-Tg mice. Aortic eNOS Ser1177 phosphorylation was enhanced ∼50% in the RBP4-KO mice, with no change in total eNOS protein. Feeding a high-fat diet increased BP in the RBP4-KO mice only to the level in the WT mice fed chow and had no effect on aortic eNOS Ser1177 phosphorylation. Ang-II infusion resulted in 22 mmHg lower systolic BP in the RBP4-KO than in the WT mice, although the relative BP increase over saline infusion was ∼30% in both. Ang-II treatment decreased aortic eNOS Ser1177 phosphorylation in the WT and RBP4-KO mice, but phosphorylation remained higher in the RBP4-KO mice. Cardiac hypertrophy with Ang-II treatment was diminished by 56% in the RBP4-KO mice. Thus, elevated serum RBP4 raises BP and lack of RBP4 reduces it, with commensurate changes in aortic eNOS Ser1177 phosphorylation. Lowering RBP4 may reduce BP through enhanced eNOS-mediated vasodilatation and may be a novel therapeutic approach for hypertension.-Kraus, B. J., Sartoretto, J. L., Polak, P., Hosooka, T., Shiroto, T., Eskurza, I., Lee, S.-A., Jiang, H., Michel, T., Kahn, B. B. Novel role for retinol-binding protein 4 in the regulation of blood pressure. FASEB J. 29, 3133-3140 (2015). www.fasebj.org

Association of Circulating Adipokines With Echocardiographic Measures of Cardiac Structure and Function in a Community‐Based Cohort

“…We observed that circulating RBP4 levels were positively associated with LVMI and LAD. These findings are in line with 2 previous experimental studies that reported an association between RBP4 and cardiac hypertrophy 9, 12. However, our observations are in contrast to another report that noted lack of any association of circulating RBP4 with echocardiographic traits (including LVM) in a moderately sized elderly cohort of men 20.…”

“…In this context, it is noteworthy that the adipose tissue is an endocrine tissue which secretes hormones (referred to as adipokines) that mediate several of the cardiometabolic consequences of obesity. Several adipokines have receptors on cardiac myocytes,7, 8, 9 exhibit prohypertrophic and antihypertrophic effects on the myocardium,10, 11, 12, 13 and have been associated with risk of overt HF 14. Prior investigations relating adipokines to cardiac structure and function have focused on single adipokines10, 11, 15, 16, 17, 18, 19, 20, 21 and related them to traditional measures of cardiac remodeling (such as LV mass [LVM]).…”

Levels of serum retinol‐binding protein 4 before and after non‐surgical periodontal treatment in lean and obese subjects: An interventional study

“…It has been shown that RBP4 is upregulated in insulin‐resistant conditions associated with obesity and provokes IR by interfering with insulin receptor substrate 1 (Gerrits et al., ; Yang et al., ). In addition, it seems to be a predictor of cardiovascular disease (Alkharfy, Al‐Daghri, Vanhoutte, Krishnaswamy, & Xu, ) and development of atherosclerosis, as it promotes atherogenic dyslipidaemia (Rocha et al., ) and is involved in the regulation of hypertension (Kraus et al., ). Recently, it has been established that RBP4 levels in gingival crevicular fluid and serum are positively correlated with body mass index (BMI) and periodontal parameters (Kanoriya, Pradeep, Mallika, Singhal, & Garg, ).…”

“…It has been shown that RBP4 is upregulated in insulin-resistant conditions associated with obesity and provokes IR by interfering with insulin receptor substrate 1 (Gerrits et al, 2012;Yang et al, 2005). In addition, it seems to be a predictor of cardiovascular disease (Alkharfy, Al-Daghri, Vanhoutte, Krishnaswamy, & Xu, 2012) and development of atherosclerosis, as it promotes atherogenic dyslipidaemia (Rocha et al, 2013) and is involved in the regulation of hypertension (Kraus et al, 2015).…”

Serum retinol‐binding protein 4 as a predictor of cardiovascular events in elderly patients with chronic heart failure

“…Previous experimental studies have revealed the pro‐hypertrophic function of RBP4 in heart. Kraus et al . found that angiotensin‐II induced cardiac hypertrophy was reduced in RBP4 knockout mice.…”