Parathyroid Hormone Has a Prosclerotic Effect on Vascular Smooth Muscle Cells

Abstract

Although accelerated atherosclerosis and arteriosclerosis are common in patients with renal failure, the pathogenesis of these changes is poorly understood. Parathyroid hormone (PTH) levels are elevated in renal failure, and have been linked to uraemic vascular changes in some studies. We examined the in vitro effects of increasing doses of the 1–34 fragment of PTH on human aortic vascular smooth muscle cells (VSMCs). Factors examined were: (1) collagen production using tritiated hydroxyproline incorporation and transcription of procollagen α₁(I) mRNA; (2) change in the surface area of collagen I lattices; (3) mRNA transcription of the collagen binding protein β1 integrin; (4) proliferation using tritiated thymidine incorporation, and (5) methyl tetrazolium salt conversion to estimate live cell number after 5 days’ exposure to PTH. PTH at a concentration of 200 pmol/l increased total collagen synthesis (188 ± 25% of control, p < 0.01) as well as transcription of procollagen α₁(I) mRNA (136 ± 11% of control, p < 0.005). PTH also increased reorganisation of collagen I lattices (surface area 47 ± 8% of well for control vs. 35.7 ± 2.5 and 34.3 ± 3.0% for PTH 100 and 200 pmol/l, respectively, p = 0.02) and upregulated β1 integrin mRNA expression (160 ± 20% of control at PTH concentration of 200 pmol/l, p < 0.05). PTH had no effect on VSMC proliferation or number at doses up to 200 pmol/l. In conclusion, PTH increases production and reorganisation of collagen by VSMCs in vitro. It is possible that more aggressive control of hyperparathyroidism in patients with renal failure may help to reduce the burden of cardiovascular disease in this patient population.

Vitamin D, Race, and Cardiovascular Mortality: Findings From a National US Sample

“…15,16 We did not assess these factors directly, although we found an inverse relationship between 25(OH)D levels and CRP.…”

“…11 Low levels of vitamin D may alter the renin-angiotensin axis by direct suppression of renin gene expression 12 ; affect vascular endothelium through smooth muscle proliferation, 13 infl ammation, 12 and thrombosis 14 ; alter calcium channel fl uxes; and induce secondary hyperparathyrodism. Elevated parathyroid hormone has been linked to mortality in the elderly, 15 possibly through vascular effects, 16 although fi ndings regarding an association with cardiovascular mortality have been mixed. 17,18 These fi ndings suggest pathways through which low levels of vitamin D may increase the risk of cardiovascular-related morbidity (including hyperten-V I TA MIN D, R AC E, A ND C A R DIOVA S CUL A R M OR TA L I T Y sion, diabetes, renal, heart and cerebrovascular disease) and subsequent cardiovascular mortality.…”

Association of Parathyroid Hormone and 25-OH-Vitamin D Levels with Arterial Stiffness in Postmenopausal Women with Vitamin D Insufficiency

“…First, PTH has been implicated in vascular calcification in the setting of end-stage renal disease 47) , and it is a well-recognized contributor to arterial stiffening 48) . Second, PTH appears to also increase total collagen synthesis and reorganized collagen in cultured vascular smooth muscle cells 49) , although PTH also prevented bovine vascular smooth muscle cell calcification in vitro 50) . Third, higher PTH levels are associated with established covariates of arterial stifness, such as hypertension, obesity and and renal dysfunction 51) ; however, the fact that PTH remained significantly associated with aortic stiffness in all multivariable models suggests that confounding by these factors is not the sole explanation for our findings.…”

Racial Disparity in Blood Pressure: is Vitamin D a Factor?

“…5 Genetic knockout models suggest vascular effects of vitamin D, including vascular endothelium, the renin-angiotensin axis, 6 and vascular smooth muscle including cell proliferation, 7 inflammation, 6 thrombosis, 8 cardiac hypertrophy, 9 and hyperparathyroid hormone secretion. 10 Prospective cohort data suggest low serum vitamin D levels might contribute to cardiovascular disease, 11 in part through elevated BP. 12 Serum vitamin D levels are largely driven by ultraviolet (UV) synthesis in the skin.…”