Vitamin D Biology in Heart Failure: Molecular Mechanisms and Systematic Review

Department of Cardiology, University Medical Center Groningen, University of Groningen, The Netherlands.
Current drug targets (Impact Factor: 3.02). 01/2011; 12(1):29-41. DOI: 10.2174/138945011793591554
Source: PubMed


Vitamin D has recently been suggested as an important mediator of blood pressure and cardiovascular disease, including heart failure. In patient with heart failure, low vitamin D levels are associated with adverse outcome and correlate with established clinical correlates and biomarkers. Many precursor states of heart failure, such as hypertension, atherosclerosis, and diabetes are more prevalent in subjects with low vitamin D levels. Recent experimental data have provided clues how vitamin D might exert cardioprotective effects. The steroid hormone vitamin D regulates gene expression of many genes that play a prominent role in the progression of heart failure, such as cytokines and hormones. Specifically, vitamin D is a negative regulator of the hormone renin, the pivotal hormone of the renin-angiotensin system. Mechanistic insights were gained by studying mice deficient for the vitamin D receptor, which develop hypertension and adverse cardiac remodeling mediated via the renin-angiotensin system. Furthermore, vitamin D receptor is expressed in the heart and regulated under pro-hypertrophic stimuli and vitamin D as receptor has been associated with the expression of other hypertrophic genes such as natriuretic peptides. So, epidemiological data and mechanistic studies have provided strong support for a potentially cardioprotective effect of vitamin D. It remains unclear if vitamin D supplementation is beneficial in preventing heart failure or if it could be a therapeutic addendum in the treatment of heart failure. This review summarizes current knowledge on vitamin D and its biology in heart failure.

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Available from: Laura Meems, May 01, 2014
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    • "Cardiac muscle is found to have vitamin D receptors (VDR) and it has been hypothesized that activation of VDR might have beneficial effects on cardiac function in animals [4] [21]. We did not see any association between Vitamin D levels and cardiac hypertrophy, which has been seen in some [22e24] but not all [25] studies. "
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    ABSTRACT: Vitamin D deficiency has been associated with increased risk for cardiovascular (CV) disease, but the possible effects of Vitamin D on cardiac structure and function are not well characterized. The correlation between 25-hydroxyvitamin D levels and metabolic and cardiac echocardiographic parameters was studied in ARTEMIS study population including 831diabetic and 659 non-diabetic patients with stable coronary artery disease (CAD). Low levels of Vitamin D were associated with high BMI (p < 0.001), high total and LDL cholesterol and triglyceride levels (p < 0.001 for all) in both diabetics and non-diabetics. Among non-diabetic patients, low Vitamin D was also associated independently with elevated systolic and diastolic blood pressure (p < 0.005). Low Vitamin D levels were independently associated with reduced left ventricular (LV) ejection fraction (p < 0.005) and increased left atrial diameter (p < 0.03) measured by cardiac ultrasound by 2-dimensional echo. In the non-diabetic group, low Vitamin D levels were associated with impaired LV filling (high E/E') (p < 0.03) and low E/A mitral flow pattern measured by Doppler echocardiography (p < 0.05). Among diabetics, low Vitamin D levels were also related to increased LV end-systolic diameter (p < 0.05) and right ventricular diameter (p < 0.005). The association between LV diastolic filling (E/E') and Vitamin D levels was significant (p < 0.01) after adjustment for the commonly recognized risk factors of diastolic dysfunction in linear regression analysis. Low Vitamin D is associated with several major cardiovascular risk factors and cardiac structural changes including impaired systolic and diastolic function, which together may explain the association of low Vitamin D to worse cardiovascular outcome. Copyright © 2015 Elsevier B.V. All rights reserved.
    Full-text · Article · Feb 2015 · Nutrition, metabolism, and cardiovascular diseases: NMCD
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    • "Genes that mediate muscle atrophy such as atrogin-1 and Murf-1, were unaltered in the heart unlike skeletal muscle; implying that cardiac wasting occurs via different molecular pathways (Zhou et al., 2010; Shum et al., 2013; Unplublished Data). Vitamin D and its gene effects in the context of functional consequences have been described in skeletal muscle cell culture models, cardiac muscle and smooth muscle (Meems et al., 2011; Girgis et al., 2014). However, the roles of VDR and 1,25-(OH)2D3 need further characterization in the context of muscle wasting due to cancer cachexia (Figure 1). "
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    ABSTRACT: Myopathy is a feature of many inflammatory syndromes. Chronic inflammation has been linked to pathophysiological mechanisms which implicate 1,25 dihydroxyvitamin D3 (1,25-(OH)2D3)-mediated signaling pathways with emerging evidence supporting a role for the vitamin D receptor (VDR) in contractile and metabolic function of both skeletal and cardiac muscle. Altered VDR expression in skeletal and cardiac muscle has been reported to result in significant effects on metabolism, calcium signaling and fibrosis in these tissues. Elevated levels of serum inflammatory cytokines, such as IL-6, TNF-α and IFNγ, have been shown to impact myogenic and nuclear receptor signaling pathways in cancer-induced cachexia. The dysregulation of nuclear receptors, such as VDR and RXRα in muscle cells, has also been postulated to result in myopathy via their effects on muscle structural integrity and metabolism. Future research directions include generating transcriptome-wide information incorporating VDR and its gene targets and using systems biology approaches to identify altered molecular networks in human tissues such as muscle. These approaches will aid in the development of novel therapeutic targeting strategies for inflammation-induced myopathies.
    Full-text · Article · Apr 2014 · Frontiers in Physiology
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    • "(R.A. de Boer). vitamin D deficiency [2] [3]. We and others have reported that vitamin D deficiency is associated with a poor prognosis in HF [2] [4]. "
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    ABSTRACT: Activation of the vitamin D-vitamin D receptor (VDR) axis has been shown to reduce blood pressure and left ventricular (LV) hypertrophy. Besides cardiac hypertrophy, cardiac fibrosis is a key element of adverse cardiac remodeling. We hypothesized that activation of the VDR by paricalcitol would prevent fibrosis and LV diastolic dysfunction in an established murine model of cardiac remodeling. Mice were subjected to transverse aortic constriction (TAC) to induce cardiac hypertrophy. Mice were treated with paricalcitol, losartan, or a combination of both for a period of four consecutive weeks. The fixed aortic constriction caused similar increase in blood pressure, both in untreated and paricalcitol- or losartan-treated mice. TAC significantly increased LV weight compared to sham operated animals (10.2±0.7 vs. 6.9±0.3mg/mm, p<0.05). Administration of either paricalcitol (10.5±0.7), losartan (10.8±0.4), or a combination of both (9.2±0.6) did not reduce LV weight. Fibrosis was significantly increased in mice undergoing TAC (5.9±1.0 vs. sham 2.4±0.8%, p<0.05). Treatment with losartan and paricalcitol reduced fibrosis (paricalcitol 1.6±0.3% and losartan 2.9±0.6%, both p<0.05 vs. TAC). This reduction in fibrosis in paricalcitol treated mice was associated with improved indices of LV contraction and relaxation, e.g. dPdtmax and dPdtmin and lower LV end diastolic pressure, and relaxation constant Tau. Also, treatment with paricalcitol and losartan reduced mRNA expression of ANP, fibronectin, collagen III and TIMP-1. Treatment with the selective VDR activator paricalcitol reduces myocardial fibrosis and preserves diastolic LV function due to pressure overload in a mouse model. This is associated with a reduced percentage of fibrosis and a decreased expression of ANP and several other tissue markers.
    Full-text · Article · Jul 2012 · The Journal of steroid biochemistry and molecular biology
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