Parathyroid hormone has a prosclerotic effect on vascular smooth muscle cells.
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 alpha(1)(I) mRNA; (2) change in the surface area of collagen I lattices; (3) mRNA transcription of the collagen binding protein beta1 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 alpha(1)(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 beta1 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.
Perkovic
Vlado
V
Department of Nephrology, University of Melbourne, The Royal Melbourne Hospital, Melbourne, Vic, Australia. vlado-perkovic@mh.org.au
Hewitson
Timothy D
TD
Kelynack
Kristen J
KJ
Martic
Marina
M
Tait
Melanie G
MG
Becker
Gavin J
GJ
D001011:Aorta / Q000166:cytology; D001161:Arteriosclerosis / Q000378:metabolism / Q000503:physiopathology; D002455:Cell Division; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D010281:Parathyroid Hormone / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D014511:Uremia / Q000378:metabolism / Q000503:physiopathology
D010281:Parathyroid Hormone; D010446:Peptide Fragments