Cutaneous Vascular Heatlh: Ultraviolet Radiation and Vitamin D/Folate Metabolism in Differently Pigmented Skin
Open Access
- Author:
- Wolf, Stephen
- Graduate Program:
- Kinesiology
- Degree:
- Doctor of Philosophy
- Document Type:
- Dissertation
- Date of Defense:
- October 12, 2020
- Committee Members:
- William Lawrence Kenney, Jr., Dissertation Advisor/Co-Advisor
William Lawrence Kenney, Jr., Committee Chair/Co-Chair
Lacy Marie Alexander, Committee Member
Nina G Jablonski, Committee Member
Sara B Ferguson, Outside Member
Martin John Sliwinski, Committee Member
Jonathan Bates Dingwell, Program Head/Chair - Keywords:
- Nitric oxide
microvascular function
folate
vitamin d
oxidative stress
endothelial function
skin pigmentation - Abstract:
- Cardiovascular disease (CVD) is the leading cause of death worldwide, and vascular endothelial dysfunction, characterized by reduced nitric oxide (NO) bioavailability, is a common antecedent. Ultraviolet radiation (UVR) may influence endothelial function via disparate effects on folate and vitamin D. Vitamin D is produced in the skin upon exposure to UVR (specifically UV-B), and may modulate endothelial function by reducing oxidative stress, increasing expression of endothelial NO synthase (eNOS), and/or reducing vascular inflammation. Conversely, UVR exposure may degrade the bioactive folate metabolite and eNOS cofactor, 5-methyltetrahydrofolate (5-MTHF), and/or increase oxidative stress and inflammation. Darkly-pigmented skin (i.e., high eumelanin concentration) may protect against deleterious effects of UVR, but impair cutaneous vitamin D biosynthesis. On the other hand, lightly-pigmented skin (i.e., low eumelanin concentration) promotes adequate vitamin D synthesis, but may be predisposed to harmful effects of UVR. This dissertation comprises two published literature reviews and three empirical studies investigating the influence of UVR, and the modulating role of skin pigmentation, on cutaneous microvascular endothelial function through its roles in 5-MTHF and vitamin D metabolism. The first study investigated the acute deleterious effects of UV-B exposure on NO-mediated cutaneous microvascular function via 5-MTHF degradation and/or production of oxidative stress. Results indicated that (1) acute UV-B exposure attenuated NO-mediated dilation in the skin microvasculature, (2) local delivery of 5-MTHF or ascorbate (non-specific antioxidant) ameliorated the effect of UV-B exposure, and (3) these effects were independent of skin pigmentation. Together, these findings suggest that UV-B exposure acutely impairs NO-mediated cutaneous microvascular function, independently of skin pigmentation, via direct and/or indirect photodegradation of 5-MTHF. The second study, consisting of two parts, examined the influence of sunscreen or a simulated sweat solution on the skin in modulating the cutaneous microvascular effects of broad-spectrum UVR (UV-A + UV-B) exposure. Part one concluded that (1) an erythemal dose of UVR resulted in a linear increase in erythema across an 8-hour post-exposure period with a delayed increase in skin blood flow, and (2) broad-spectrum SPF-50 sunscreen blunted skin erythema and blood flow responses post-exposure. Part two determined that (1) acute exposure of the skin to a sub-erythemal dose of broad-spectrum UVR attenuated NO-mediated vasodilation in response to a local skin heating stimulus, but (2) sunscreen or simulated sweat on the skin during exposure was protective against those deleterious effects of UVR exposure. These data suggest that although a sub-erythemal dose of broad-spectrum UVR attenuates NO-mediated vasodilation during local heating, an erythemal dose is necessary to elicit an inflammatory increase in resting skin blood flow, while sunscreen on the skin during exposure is protective of both responses. The third study investigated the efficacy of four weeks of 2,000 IU/day oral vitamin D supplementation for ameliorating oxidative stress-induced cutaneous microvascular dysfunction in college-aged, darkly-pigmented African Americans (AA). That study established that (1) serum 25(OH)D concentrations were lower in AA compared to their lightly-pigmented European American (EA) counterparts, (2) the magnitude of the response to local skin heating, as well as the NO-mediated component of that response, were lower in AA compared to EA, (3) local delivery of tempol (a superoxide dismutase mimetic), but not apocynin (an NADPH oxidase inhibitor), improved cutaneous microvascular responses to local heating in AA before vitamin D supplementation, and (4) vitamin D supplementation improved serum 25(OH)D concentrations and mitigated the differences in microvascular responses to local heating between groups. The findings of this study suggest that ensuring adequate vitamin D status in otherwise healthy, young AA may provide an effective strategy to mitigate the development of oxidative stress-induced cutaneous microvascular dysfunction. Together, these three studies provide mechanistic insight into both beneficial and deleterious effects of UVR exposure on cutaneous microvascular function, suggesting (1) a balance between healthy and unhealthy amounts of UVR exposure that may differ based on varying degrees of skin pigmentation, and (2) a beneficial role for vitamin D supplementation in young African Americans.