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Serum from young, sedentary adults who underwent passive heat therapy improves endothelial cell angiogenesis via improved nitric oxide bioavailability.

ABSTRACT: Rationale: Passive heat therapy improves vascular endothelial function, likely via enhanced nitric oxide (NO) bioavailability, although the mechanistic stimuli driving these changes are unknown. Objective: To determine the isolated effects of circulating (serum) factors on endothelial cell function, particularly angiogenesis, and NO bioavailability. Methods and Results: Cultured human umbilical vein endothelial cells (HUVECs) were exposed to serum collected from 20 healthy young (22 ± 1 years) adults before (0 wk), after one session of water immersion (Acute HT), and after 8 wk of either heat therapy (N = 10; 36 sessions of hot water immersion; session 1 peak rectal temperature: 39.0 ± 0.03°C) or sham (N = 10; 36 sessions of thermoneutral water immersion). Serum collected following acute heat exposure and heat therapy improved endothelial cell angiogenesis (Matrigel bioassay total tubule length per frame, 0 wk: 69.3 ± 1.9 mm vs. Acute HT: 72.8 ± 1.4 mm, p = 0.04; vs. 8 wk: 73.0 ± 1.4 mm, p = 0.03), with no effects of sham serum. Enhanced angiogenesis was NO-mediated, as addition of the NO synthase (NOS) inhibitor L-NNA to the culture media abolished differences in tubule formation across conditions (0 wk: 71.3 ± 1.8 mm, Acute HT: 71.6 ± 1.9 mm, 8 wk: 70.5 ± 1.6 mm, p = 0.69). In separate experiments, we found that abundance of endothelial NOS (eNOS) was unaffected by Acute HT serum (p = 0.71), but increased by 8 wk heat therapy serum (1.4 ± 0.1-fold from 0 wk, p < 0.01). Furthermore, increases in eNOS were related to improvements in endothelial tubule formation (r2 = 0.61, p < 0.01). Conclusions: Passive heat therapy beneficially alters circulating factors that promote NO-mediated angiogenesis in endothelial cells and increase eNOS abundance. These changes may contribute to improvements in vascular function with heat therapy observed in vivo. Abbreviations: Ang-1: angiopoietin-1; ANOVA: analysis of variance; bFGF: basic fibroblast growth factor; CV: cardiovascular; CVD: cardiovascular diseases; eNOS: endothelial nitric oxide synthase; HSPs: heat shock proteins; HT: heat therapy; HUVECs: human umbilical endothelial cells; L-NNA: N?-nitro-L-arginine; MnSOD: manganese superoxide dismutase; NO: nitric oxide; NOS: nitric oxide synthase; PBMCs: peripheral blood mononuclear cells; RM: repeated measures; sFlt-1: soluble VEGF receptor; SOD: superoxide dismutase; TGF-?: transforming growth factor- ?; VEGF: vascular endothelial growth factor.

SUBMITTER: Brunt VE

PROVIDER: S-EPMC6601412 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Serum from young, sedentary adults who underwent passive heat therapy improves endothelial cell angiogenesis via improved nitric oxide bioavailability.

Brunt Vienna E VE Weidenfeld-Needham Karen M KM Comrada Lindan N LN Francisco Michael A MA Eymann Taylor M TM Minson Christopher T CT

Temperature (Austin, Tex.) 20190516 2

Rationale: Passive heat therapy improves vascular endothelial function, likely via enhanced nitric oxide (NO) bioavailability, although the mechanistic stimuli driving these changes are unknown. Objective: To determine the isolated effects of circulating (serum) factors on endothelial cell function, particularly angiogenesis, and NO bioavailability. Methods and Results: Cultured human umbilical vein endothelial cells (HUVECs) were exposed to serum collected from 20 healthy y ...[more]

PMID: 31286027

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Project description:BackgroundHypertension is a major cause of death worldwide. Although arsenic exposure has been associated with the risk of hypertension, this association appears nonuniform due to inconsistent results from studies conducted in different populations. Moreover, hypertension is a complex condition with multiple underlying mechanisms and factors. One factor is impaired production and bioavailability of vascular nitric oxide (NO). However, the implications of the effects of arsenic exposure on circulating NO and its association with hypertension in humans are largely unknown.ObjectiveWe investigated the dose-response relationship between arsenic exposure and hypertension with vascular NO levels as a potential mediator of arsenic-related hypertension in individuals exposed to a broad range of arsenic.MethodsA total of 828 participants were recruited from low- and high-arsenic exposure areas in Bangladesh. Participants' drinking water, hair, and nail arsenic concentrations were measured by inductively coupled plasma mass spectroscopy. Hypertension was defined as a systolic blood pressure (SBP) value of ≥140 and a diastolic (DBP) value of ≥90 mmHg. Serum NO levels reflected by total serum nitrite concentrations were measured by immunoassay. A formal causal mediation analysis was used to assess NO as a mediator of the association between arsenic level and hypertension.ResultsIncreasing concentrations of arsenic measured in drinking water, hair, and nails were associated with the increasing levels of SBP and DBP. The odds of hypertension were dose-dependently increased by arsenic even in participants exposed to relatively low to moderate levels (10-50μg/L) of water arsenic [odds ratios (ORs) and 95% confidence intervals (CIs): 2.87 (95% CI: 1.28, 6.44), 2.67 (95% CI: 1.27, 5.60), and 5.04 (95% CI: 2.71, 9.35) for the 10-50μg/L, 50.01-150μg/L, and >150μg/L groups, respectively]. Causal mediation analysis showed a significant mediating effect of NO on arsenic-related SBP, DBP, and hypertension.ConclusionIncreasing exposure to arsenic was associated with increasing odds of hypertension. The association was mediated through the reduction of vascular NO bioavailability, suggesting that impaired NO bioavailability was a plausible underlying mechanism of arsenic-induced hypertension in this Bangladeshi population. https://doi.org/10.1289/EHP13018.

Dataset Information

Serum from young, sedentary adults who underwent passive heat therapy improves endothelial cell angiogenesis via improved nitric oxide bioavailability.

Publications

Serum from young, sedentary adults who underwent passive heat therapy improves endothelial cell angiogenesis via improved nitric oxide bioavailability.

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