Down-regulation of calpain 9 is linked to hypertensive heart and kidney disease.
Calpains are a family of 14 intracellular calcium-dependent proteases, which have been implicated in cardiovascular diseases. We aimed to analyze specifically the expressional regulation of the different calpain isoforms in hypertensive target organ damage. Using real-time PCR, we found calpain 6 and 9 down-regulated by more than 50% and the endogenous calpain inhibitor calpastatin up-regulated by 225%, respectively, in the hearts of Dahl salt-sensitive rats on a high salt (4% NaCl) compared to normal salt diet. On the protein level, calpain 9 but not calpastatin was regulated in the hypertensive target organs heart and kidney. Moreover, the myocardial expression of calpain 9 protein was inversely linked to left ventricular mass (r= -0.93, p<0.01), and renal expression of calpain 9 protein correlated inversely with albuminuria (r= -0.82, p<0.05). In the aorta, there was no regulation of calpain 9 on the protein level. We conclude that differential regulation of calpain 9 may play a role in hypertensive target organ damage.
Markmann
André
A
Aventis Pharma Deutschland GmbH, DG Cardiovascular Diseases, Building H825, Industriepark Höchst, Frankfurt am Main, Germany.
Schäfer
Stefan
S
Linz
Wolfgang
W
Löhn
Matthias
M
Busch
Andreas E
AE
Wohlfart
Paulus
P
D000818:Animals; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D002154:Calpain / Q000235:genetics* / Q000378:metabolism*; D015536:Down-Regulation; D015971:Gene Expression Regulation, Enzymologic; D006331:Heart Diseases / Q000150:complications / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D006352:Heart Ventricles / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D006973:Hypertension / Q000150:complications / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D007674:Kidney Diseases / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D020303:Rats, Inbred Dahl
D002135:Calcium-Binding Proteins; D007527:Isoenzymes; D012333:RNA, Messenger; C033668:calpastatin; D002154:Calpain