Vitamin D as A Protector of Arterial Health: Potential Role in Peripheral Arterial Disease Formation

Abstract

Atherosclerotic occlusive diseases and aneurysms that affect large and medium-sized arteries outside the cardiac and cerebral circulation are collectively known as peripheral arterial disease (PAD). With a rise in the rate of aging population worldwide, the number of people diagnosed with PAD is rapidly increasing. The micronutrient vitamin D is an important steroid hormone that acts on many crucial cellular mechanisms. Experimental studies suggest that optimal levels of vitamin D have beneficial effects on the heart and blood vessels; however, high vitamin D concentrations have been implicated in promoting vascular calcification and arterial stiffness. Observations from various clinical studies shows that deficiency of vitamin D has been associated with a greater risk of PAD. Epidemiological studies have often reported an inverse relation between circulating vitamin D status measured in terms of 25-hydroxivitamin D [25(OH)D] levels and increased cardiovascular disease risk; however, randomized controlled trials did not show a consistent positive effect of vitamin D supplementation on cardiovascular disease risk or events. Even though PAD shares all the major risk factors with cardiovascular diseases, the effect of vitamin D deficiency in PAD is not clear. Current evidence suggests a strong role of vitamin D in promoting genomic and epigenomic changes. This review summarises the current literature that supports the notion that vitamin D deficiency may promote PAD formation. A better understanding of underlying pathological mechanisms will open up new therapeutic possibilities which is the main unmet need in PAD management. Furthermore, epigenetic evidence shows that a more holistic approach towards PAD prevention that incorporates a healthy lifestyle, adequate exercise and optimal nutrition may be more effective in protecting the genome and maintaining a healthy vasculature.

Vitamin D and Cardiovascular Risk: Which Implications in Children?

“…Over the years, several observational studies in adults have found an association between low vitamin D levels and higher blood pressure levels, myocardial infarction, heart failure, coronary heart disease, peripheral arterial disease, and atherosclerosis [21,44,45].…”

VDR Gene Polymorphisms in Healthy Individuals with Family History of Premature Coronary Artery Disease

“…VitD has metabolic activity through the VDR receptor whose gene is located on chromosome 12q12-q14 [ 38 ]. VDR binds the active form of VitD (calcitriol), which causes interaction with the retinoid X receptor ( RXR ), thus forming a VDR / RXR /cofactor complex that binds to the elements of the VitD response element ( VDRE ) in the gene's promoter region.…”

“…VDR binds the active form of VitD (calcitriol), which causes interaction with the retinoid X receptor ( RXR ), thus forming a VDR / RXR /cofactor complex that binds to the elements of the VitD response element ( VDRE ) in the gene's promoter region. This leads to activation or suppression of expression by interacting with additional coregulators [ 38 – 40 ]. The VDR protein is expressed in many types of cells in the human organism [ 22 ].…”

“…Confirmation that VDR is present in most cells of the human body suggests that polymorphic changes within it may affect development of many diseases, including CAD [ 22 , 42 ]. Published studies show a beneficial role of VitD in CVD by regulating factors associated with increased risk for atherosclerosis, such as plasminogen-1 activator inhibitor in human aortic smooth muscle cells [ 12 , 38 , 39 , 43 ].…”

Nutrition, dietary habits, and weight management to prevent and treat patients with peripheral artery disease

“…Hypovitaminosis D has been associated with higher prevalence and severity of PAD disease. The potential mechanism is explained by the fact that hyperparathyroidism increases the risk of osteomalacia and arterial calcification (Krishna, 2019). Folate and vitamin D deficiencies have been linked to an increased risk of PAD and worsening ambulatory sta-tus (Kokkinidis et al, 2020a).…”