Left ventricular periostin gene expression is associated with fibrogenesis in experimental renal insufficiency

• Published in: Nephrology, dialysis, transplantation Vol. 27; no. 1; pp. 115 - 122
• Main Authors: POHJOLAINEN, Virva, RYSÄ, Jaana, NÄPÄNKANGAS, Juha, KÖÖBI, Peeter, ERÄRANTA, Arttu, ILVES, Mika, SERPI, Raisa, PÖRSTI, Ilkka, RUSKOAHO, Heikki
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 2012
• Subjects: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Biological and medical sciences; Biomarkers - metabolism; Blotting, Western; Bone Density Conservation Agents - pharmacology; Calcinosis; Cell Adhesion Molecules - genetics; Cell Adhesion Molecules - metabolism; Disease Models, Animal; Emergency and intensive care: renal failure. Dialysis management; Ergocalciferols - pharmacology; Fibrosis - etiology; Fibrosis - metabolism; Fibrosis - pathology; Gene Expression; Heart Ventricles - metabolism; Hypertension - genetics; Hypertension - metabolism; Hypertension - pathology; Immunoenzyme Techniques; Intensive care medicine; Kidney Function Tests; Medical sciences; Myocardial Infarction - genetics; Myocardial Infarction - metabolism; Myocardial Infarction - pathology; Nephrectomy - adverse effects; Nephrology. Urinary tract diseases; Nephropathies. Renovascular diseases. Renal failure; Rats; Rats, Inbred SHR; Rats, Sprague-Dawley; Real-Time Polymerase Chain Reaction; Renal failure; Renal Insufficiency - complications; Renal Insufficiency - metabolism; Renal Insufficiency - pathology; RNA, Messenger - genetics; Kidney disease; Hypertension; Urinary system disease; Hemodialysis; periostin; Cardiovascular disease; Gene expression; Left ventricle; Extrarenal dialysis; cardiac remodelling; Fibrosis; Renal failure; chronic renal insufficiency
• ISSN: 0931-0509; 1460-2385
• DOI: 10.1093/ndt/gfr279

Cardiovascular diseases are the most important cause of death in patients with impaired kidney function. Left ventricular hypertrophy (LVH), cardiac interstitial fibrosis and cardiovascular calcifications are characteristic of chronic renal insufficiency (CRI). Periostin is a fibrogenesis- and calcification-related matricellular protein re-expressed in adult tissues undergoing remodelling in response to pathological stimuli. The role of periostin in CRI-induced LVH is unknown. Rats were 5/6-nephrectomized (NX), and after 15 weeks of disease progression high-calcium, high-phosphate or paricalcitol treatment was given for 12 weeks. Cardiac tissue and blood samples were taken to study periostin gene expression and to determine factors contributing to its reactivation, respectively. Left ventricular (LV) periostin expression was also examined in response to angiotensin II or arginine(8)-vasopressin (AVP)-induced pressure overload and in spontaneously hypertensive rats. CRI resulted in a 6.5-fold increase in LV periostin messenger RNA (mRNA) levels. Positive extracellular immunostaining for periostin was detected in areas of infiltrated inflammatory cells and fibrotic lesions. There was a significant correlation between LV periostin mRNA levels and plasma biomarkers of impaired kidney function, LVH, fibrogenesis-related proteins osteopontin and osteoactivin, and anti-calcific matrix Gla protein. Moreover, LV periostin gene expression in CRI correlated positively with systolic blood pressure (BP) and was activated rapidly in response to angiotensin II or AVP infusions. Periostin is involved in fibrotic cardiac remodelling in CRI. The re-expression of periostin is localized to the fibrotic and inflammatory lesions and is most likely the consequence of elevated BP.