1. Parathyroid Hormone Has a Prosclerotic Effect on Vascular Smooth Muscle Cells
- Author
-
Marina Martic, Melanie G. Tait, Kristen J. Kelynack, Vlado Perkovic, Gavin J. Becker, and Tim D. Hewitson
- Subjects
medicine.medical_specialty ,Contraction (grammar) ,Vascular smooth muscle ,Cell division ,Arteriosclerosis ,Parathyroid hormone ,In Vitro Techniques ,Muscle, Smooth, Vascular ,Pathogenesis ,Fibrosis ,Internal medicine ,medicine ,Humans ,In patient ,skin and connective tissue diseases ,Aorta ,Cells, Cultured ,Uremia ,Accelerated atherosclerosis ,business.industry ,General Medicine ,medicine.disease ,Peptide Fragments ,Extracellular Matrix ,Endocrinology ,Parathyroid Hormone ,Nephrology ,sense organs ,Cardiology and Cardiovascular Medicine ,business ,Cell Division ,hormones, hormone substitutes, and hormone antagonists - 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.
- Published
- 2003