Article

Cardiac hypertrophy in vitamin D receptor knockout mice: role of the systemic and cardiac renin-angiotensin systems.

Department of Medicine, University of Chicago, Chicago, IL 60637, USA.
AJP Endocrinology and Metabolism (Impact Factor: 4.09). 02/2005; 288(1):E125-32. DOI: 10.1152/ajpendo.00224.2004
Source: PubMed

ABSTRACT Our recent studies suggest that 1,25-dihydroxyvitamin D3 functions as an endocrine suppressor of renin biosynthesis. Genetic disruption of the vitamin D receptor (VDR) results in overstimulation of the renin-angiotensin system (RAS), leading to high blood pressure and cardiac hypertrophy. Consistent with the higher heart-to-body weight ratio, the size of left ventricular cardiomyocytes in VDR knockout (KO) mice was markedly increased compared with wild-type (WT) mice. As expected, levels of atrial natriuretic peptide (ANP) mRNA and circulating ANP were also increased in VDRKO mice. Treatment of VDRKO mice with captopril reduced cardiac hypertrophy and normalized ANP expression. To investigate the role of the cardiac RAS in the development of cardiac hypertrophy, the expression of renin, angiotensinogen, and AT-1a receptor in the heart was examined by real-time RT-PCR and immunostaining. In VDRKO mice, the cardiac renin mRNA level was significantly increased, and this increase was further amplified by captopril treatment. Consistently, intense immunostaining was detected in the left ventricle of captopril-treated WT and VDRKO mice by use of an anti-renin antibody. Levels of cardiac angiotensinogen and AT-1a receptor mRNAs were unchanged in the mutant mice. These data suggest that the cardiac hypertrophy seen in VDRKO mice is a consequence of activation of both the systemic and cardiac RAS and support the notion that 1,25-dihydroxyvitamin D(3) regulates cardiac functions, at least in part, through the RAS.

0 Followers
 · 
96 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: The global population is aging. Cardiovascular disease is the leading cause of death in both men and women older than 65 years. In particular, elderly patients have an increased prevalence of left ventricular hypertrophy (LVH) and chronic kidney disease (CKD), both of which predict increased cardiovascular morbidity and mortality. LVH and CKD frequently coexist in the elderly, and LVH is a powerful predictor of mortality in patients with end-stage renal disease. Several hemodynamic factors contribute to LVH and CKD in the elderly. Increased arterial stiffness in the elderly is associated with LVH and CKD. Studies using noninvasive measures of arterial stiffening have shown a correlation between these measures and LVH in patients with CKD. Hypertensive patients with an altered circadian blood pressure pattern such as nondippers have an increased incidence of LVH and CKD. Anemia is a risk factor for LVH in patients in all stages of CKD, and studies have shown correlations between age, anemia and LV mass. Nonhemodynamic factors include chronic inflammation, increased oxidative stress, and reduced autophagy, all of which are present in the elderly. Disordered mineral metabolism in the elderly with reduced levels of vitamin D and elevated levels of parathyroid hormone and phosphorus is associated with LVH and CKD. Multiple pathophysiologic mechanisms contribute to the development of LVH and CKD in the elderly. Future research should be directed at interfering with this development and reducing the burden of cardiovascular and renal diseases in this growing population.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Objective: To analyze the vitamin D status and its relationship with metabolic syndrome (MS) risk factors in a group of Spanish schoolchildren. Material and methods: A group of 314 Spanish schoolchildren (8-13 years old) from A Coruna, Barcelona, Madrid, Seville and Valencia were studied. Anthropometric data on weight, height, waist and hip circumferences, and triceps skinfold, as well as blood pressure data were collected. Serum levels of glucose, triglycerides, HDL-c and 25-hydroxycholecalciferol (25 (OH) D) were assessed. Following Cook criterion, the following MS risk factors were defined: glucose ≥100 mg/dL; ≥P90 waist circumference; triglycerides> P90, HDL ≤P10; and sistolic and/or diastolic blood pressure > P90. Results: Mean serum 25(OH)D were 23.0}8.6 ng/mL. Forty seven percent of children had hypovitaminosis (20- 30 ng/mL) and 35% had vitamin deficiency ( Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Serum 25-hydroxyvitamin D (25OHD) deficiency (<50 nmol/l or 20ng/ml) has been associated with increased blood pressure (BP) in observational studies. A paucity of data on this relationship is available in Latin American or child populations. This study investigates the association between 25OHD levels and BP in adolescents at risk for vitamin D deficiency in 2 Peruvian settings. In a population-based study of 1,441 Peruvian adolescents aged 13-15 years, 1,074 (75%) provided a serum blood sample for 25OHD analysis and BP measurements. Relationships between 25OHD and BP metrics were assessed using multiple linear regressions, adjusted for anthropometrics and sociodemographic factors. 25OHD deficiency was associated with an elevated diastolic BP (DBP) (1.09mm Hg increase, 95% confidence interval: 0.04 to 2.14; P = 0.04) compared to nondeficient adolescents. Systolic BP (SBP) trended to increase with vitamin D deficiency (1.30mm Hg increase, 95% confidence interval: -0.13 to 2.72; P = 0.08). Mean arterial pressure (MAP) was also greater in adolescents with 25OHD (1.16mm Hg increase, 95% confidence interval: 0.10 to 2.22; P = 0.03). SBP was found to demonstrate a U-shaped relationship with 25OHD, while DBP and MAP demonstrated inverse J-shaped relationships with serum 25OHD status. The association between 25OHD deficiency and BP was not different across study sites (all P ≥ 0.19). Adolescents deficient in 25OHD demonstrated increased DBP and MAP and a trend toward increased SBP, when compared to nondeficient subjects. 25OHD deficiency early in life was associated with elevated BP metrics, which may predispose risk of hypertension later in adulthood. © American Journal of Hypertension, Ltd 2015. All rights reserved. For Permissions, please email: journals.permissions@oup.com.