Sr. no Topic Role of Vitamin D in Arterial Stiffness Role of Vitamin D in Oxidative stress Role of Vit D Endothelial Dysfunction Role of Vit D Stroke Role of vit D in Vascular calcification Role of Vit D in Atherosclerosis Role of Vit D in Vascular inflammation Role of Vit D in Erectile dysfunction Role of Vit D in Insulin resistance Role of Vit D in Myocardial Infarction Vit D & Pulse wave velocity Vit D & Telomerase Activity Month Apr 15 May 15 Jun 15 Jul 15 Aug 15 Sep 15 Oct 15 Nov 15 Dec 15 Jan 16 Feb 16 Mar 16

Burden of CV diseases in the elderly  Cardiovascular diseases are the most common cause of death among the elderly patients.  Age-specific mortality rates from heart disease and stroke increase exponentially with age throughout the later years of life  CV diseases account for more than 40% of all deaths among people aged 65 – 74 years and almost 60% at age 85 years and older.

Postulated mechanisms involved in vascular aging process  Oxidative stress  Activation of inflammatory pathways  Impairment of the NO pathway  Telomeres length  Telomerase activity Cellular senescence Vascular Agin Different signalling pathways involved Accumulation of senescent cells Cellular turnover mechanisms

Oxidative Stress and Endothelial Dysfunction in Aging  Increased production of reactive oxygen species due to an increased activity of NAD(P)H oxidases leads to endothelial dysfunction in aging.  Oxidative stress promotes the development of coronary artery disease and stroke in the elderly patients.  Nitric oxide (NO) is a crucial factor for the health and function of endothelial cells.  One of the consequences of increased oxidative stress in aging is a functional inactivation of NO by high concentrations of O2−resulting in significant vasomotor dysfunction.

Oxidative Stress and Endothelial Dysfunction in Aging.  In particular, impaired bioavailability of NO due to age-related oxidative stress in the coronary circulation and other vascular beds results in a severe impairment of flow/shear stress – induced vasodilation.  It compromises minute-to-minute adjustments of blood flow in response to tissue oxygen demand.

Therapeutic strategies to delay vascular aging

Healthy diet can prevent aging  Healthy diet which includes fish, vegetables, fruit, whole grains, legumes, olive oil, and less red meat and dairy products can prevent vascular aging.  Changes in lifestyle habits, such as diet and moderate exercise, can influence vascular repair mechanisms.  Healthy diet and exercise induce a reduction in cell damage and endothelial dysfunction, both of which are factors responsible for reducing cardiovascular risk in the elderly.  Consumption of flavonoid-rich foods can improve endothelial function in patients with manifest cardiovascular and cerebrovascular disease

Antioxidant supplementation  Antioxidant supplementation can play an important role in delaying or reducing many of the adverse effects of aging.  In this regard, it is interesting to review the beneficial effects that can be obtained through nutrition in the prevention of the deleterious effects induced by oxidative stress.  Repair or prevention effects have been attributed to the presence of antioxidants, mainly contained in plant foods.  Several studies indicate that vitamin D supplementation can improve antioxidant activity of cell membranes in elderly subjects.

Novel anti-inflammatory treatments  It is significant that chronic anti-TNF α treatment (eg, etanercept, which binds and inactivates TNF α) exerts multifaceted vasculoprotective effects.  It includes a significant reduction in endothelial apoptosis, downregulation of NAD(P)H oxidases, and an improvement in endothelial function in aged rats.  Whether anti-TNF a treatments can confer similar vasoprotective effects in healthy ” aging in humans is still unclear.

GH/IGF-1 supplementation  IGF-1 is an important protective factor in the cardiovascular system.  GH and IGF-I deficiency is associated with premature atherosclerosis and elevated cardiovascular disease mortality.  The available data support the conclusion that supplementation of IGF-1 may exert vasculoprotective effects in aging, improving cardiac diastolic function, and preventing hippocampal microvascular rarefaction.  IGF-1 was also shown to protect cardiac myocytes from apoptotic cell death and to promote cardiac stem cell survival and proliferation.

Proposed scheme for the mechanisms by which IGF-1 confers vasoprotective action

Caloric restriction  Caloric restriction (CR) is a dietary regimen, which improves health and slows the aging process in evolutionarily distant organisms by limiting dietary energy intake.  CR confers vasoprotection in aging and in pathological conditions associated with accelerated vascular aging.  Resveratrol (3,5,4 ′ -trihydroxystilbene), a diet-derived polyphenol, is a prototype of a new class of drugs referred to as CR mimetics.

Proposed scheme for the mechanisms by which CR confers vasoprotective action

Aging and valve disease  HVD develops and progresses with age.  Aging results in reduced outdoor activity, food intake, and vitamin D synthesis in the skin.  The nutritional intake of vitamin D is often too low to compensate for reduced dermal vitamin D synthesis.  Vitamin D synthesis in the skin usually contributes 80–90% of the vitamin D required by a healthy person.

Significance of Vitamin D  The cellular actions of vitamin D are mediated by the membrane- bound and cytosolic vitamin D receptors (VDR).  VDR is nearly universally expressed, and nearly all cells react to vitamin D exposure.  Calcitriol exerts important physiological effects on cardiomyocytes, smooth muscle cells, and the vascular endothelium.  High vitamin D status is associated with approximately 50% lower cardiovascular morbidity and mortality risk compared with low vitamin D status.

Role of parathyroid hormone levels in HVD  Patients with secondary hyperparathyroidism demonstrate a high incidence of cardiac hypertrophy, calcium deposits in the myocardium, and aortic and mitral valve calcification.  These patients may be at higher risk of death from cardiovascular system diseases.  Calcium deposits in the myocardium are found in 74% of patients

Oxidative stress and HVD  Oxidative stress is a key player in the progression of HVD.  Most especially, high oxidative stress is involved in hypovitaminosis D and the progression of cardiovascular damage.  Circulating calcidiol is an indicator of vitamin D status.  As needed, calcidiol is converted to its active hormonal form, calcitriol in the kidneys, a process that is usually tightly controlled by parathormone (PTH).  PTH levels start rising at ≤ 20 calcidiol ng/ml.

Published data  Eren et al, assessed serum 25(OH) vitamin D (calcidiol), parathormone (PTH), and redox balance in patients with mitral valve regurgitation (MR) and aortic valve regurgitation (AR).  The trial include D 56 chronic heart valve disease (HVD) patients.  40 sex-matched healthy control participants were enrolled for comparison.  Serum calcidiol, PTH, total oxidative status (TOS), and total antioxidative capacity were measured, and the oxidative stress index (OSI) was calculated.

Contd..  Results  Patients with HVD demonstrated significantly higher PTH, increased TOS and OSI, and a higher frequency of calcidiol deficiency than the control participants.  Calcidiol and TOS were negatively correlated (r = −0.29; P <0.005), as were calcidiol and OSI (r = −0.413; P = 0.001)  PTH and OSI were positively correlated (r = 0.22; P = 0.02).

Calcidiol, PTH and oxidative stress in HVD patients

Graphics of significant correlations

Conclusion of the study  Vitamin D deficiency and secondary increases in PTH are highly prevalent.  Heart valve regurgitation is also correlated with oxidative stress and more common in hypovitaminosis D patients.  Adequate calcidiol levels may promote cardiovascular health by improving endothelial function and downregulating inflammation.  In addition, calcitriol modulates endothelial and nitric oxide functions in the heart valves.  Oxidative modification of LDL by free oxygen radicals reportedly influences the initiation and progression of valve lesions.

The effect of short term vitamin d supplementation on the inflammatory and oxidative mediators of arterial stiffness  Vitamin D deficiency has been implicated as a potential risk factor for cardiovascular disease.  Vitamin D supplementation may reduce the risk of cardiovascular disease.  Vitamin D ameliorates the onset and progression of arterial stiffness, usually assessed by pulse wave velocity and augmentation index.

Contd..  In the present study, the authors evaluated the effect of a monthly dose of 100,000 IU of vitamin D3 for three months on the level of serum 25(OH)D, intact PTH, urinary isoprostane, adipocyte cytokine expression and arterial stiffness among 130 overweight and obese (BMI > 25) patients with elevated blood pressure ( / mmHg) and low serum vitamin D level ( ng/ml).

Results  There was a significant increase in the serum 25(OH)D levels to a mean level of 34.5 ng/ml (SD = 7.1) with the intervention (p < 0.001).  The increase in 25(OH)D levels was associated with a significant decrease in the serum level of intact PTH (p = 0.02), mean urinary isoprostane (p = 0.02) and adipocyte cytokine expression.  It was also associated with a significant decrease in the augmentation index among the participants with the highest tertile of urinary isoprostane (p = 0.007).  Conclusion: Vitamin D supplementation increased serum 25(OH)D levels, decreased intact PTH level and the levels of select inflammatory and oxidative stress mediators of arterial stiffness.

Ability of vitamin D to inhibit iron-dependent lipid peroxidation in liposomes and relevance to anticancer action  Vitamin D is a membrane antioxidant.  Vitamin D3 and its active metabolite 1,25-dihydroxycholecalciferol and also Vitamin D2 and 7-dehydrocholesterol all inhibited iron- dependent liposomal lipid peroxidation.  Cholecalciferol, 1,25- dihydroxycholecalciferol and ergocalciferol were all of similar effectiveness as inhibitors of lipid peroxidation but were less effective than 7- dehydrocholesterol; this was a better inhibitor of lipid peroxidation than cholesterol, though not ergosterol.  The structural basis for the antioxidant ability of these Vitamin D compounds is considered in terms of their molecular relationship to cholesterol and ergosterol.

Conclusion of the study  The hormonal form is recognised to be the active form of Vitamin D for calcium and phosphorus metabolism in the human body.  It has an antioxidant ability, which may be of importance in protecting the membranes of normal cells against free radical- induced oxidative damage.   Vitamin D could help inhibit the growth of cancer cells by decreasing membrane fluidity by the membrane interaction that is thought to lead to the observed inhibition of lipid peroxidation.

Summary  Oxidative stress promotes the development of coronary artery disease.  Decreased endothelial NO production in aging promotes apoptosis of endothelial cells and leads to microvascular.  Anti oxidant therapy to treat vascular aging.  Role of Vitamin D in Oxidative stress.