Serum from patients with chronic renal insufficiency alters growth characteristics and ANP mRNA expression of adult rat cardiac myocytes.
Left ventricular hypertrophy is very prevalent among patients with renal insufficiency. Known hypertrophic factors, such as systemic hypertension, do not adequately account for the prevalence of left ventricular hypertrophy in these patients. Circulating growth factors may stimulate cardiomyocyte growth and contribute to the development of left ventricular hypertrophy. The effects of sera from patients with (n = 30) and without (n = 5) chronic renal insufficiency on the growth of cultured adult cardiomyocytes were compared. An adult rat cardiomyocyte primary culture system was established with a high purity of cardiomyocyte population as confirmed by immunocytochemical staining of cardiac contractile proteins. Myocytes responded with increased [3H]thymidine incorporation when treated with angiotensin II, epidermal growth factor, hydrocortisone and insulin, and with increased [3H]phenylalanine incorporation when treated with parathormone, isoproterenol, phenylephrine and insulin. Renal insufficiency serum stimulated [3H]thymidine incorporation was 1.5 times that of the control (P < 0.02) and also tended to increase incorporation of [3H]phenylalanine compared to the control (P = N.S.). Increased [3H]thymidine incorporation by renal insufficiency serum did not correlate with serum insulin, parathormone or glucose in the renal insufficiency patients. A quantitative reverse transcriptase polymerase chain reaction (RT-PCR) method was used to measure renal insufficiency serum-induced atrial natriuretic peptide mRNA expression in cultured cardiomyocytes. Atrial natriuretic peptide (ANP) mRNA was increased 1-3-fold in cardiomyocytes treated with renal insufficiency sera in comparison to control sera. These data suggest that circulating growth factor(s) may contribute to the development of cardiac hypertrophy in patients with renal insufficiency.
Yu
J Z
JZ
Department of Pathology and Laboratory Medicine, St. Paul's Hospital-University of British Columbia, Vancouver, Canada.
Bondy
G P
GP
Allard
M F
MF
Thompson
C R
CR
Levin
A
A
McManus
B M
BM
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000235:genetics* / Q000378:metabolism; D002455:Cell Division; D002478:Cells, Cultured; D015870:Gene Expression; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000097:blood*; D008297:Male; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D010649:Phenylalanine / Q000493:pharmacokinetics; D012333:RNA, Messenger; D051381:Rats; D017207:Rats, Sprague-Dawley; D013936:Thymidine / Q000493:pharmacokinetics; D014316:Tritium
D006133:Growth Substances; D012333:RNA, Messenger; D014316:Tritium; D010649:Phenylalanine; D009320:Atrial Natriuretic Factor; D013936:Thymidine