Induction of mitogen-activated protein kinases is proportional to the amount of pressure overload.
Pressure overload has been shown to induce mitogen activated protein kinases (MAPKs) and reactivate the atrial natriuretic factor in the heart. To test the sensitivity of these signals to pressure overload, we assayed the activity of MAPKs extracellular signal-regulated kinase, c-Jun N-terminal kinase 1, and p38 in protein lysates from the left ventricle (LV) or white blood cells (WBC) isolated from aortic banded mice with varying levels of pressure overload. In separated mice we measured atrial natriuretic factor mRNA levels by Northern blotting. As expected, a significant induction of atrial natriuretic factor mRNA levels was observed after aortic banding, and it significantly correlated with the trans-stenotic systolic pressure gradient but not with the LV weight:body weight ratio. In contrast, a significant correlation with systolic pressure gradient or LV weight:body weight ratio was observed for all of the MAPK activity detected in LV samples or WBCs. Importantly, LV activation of MAPKs significantly correlated with their activation in WBCs from the same animal. To test whether MAPK activation in WBCs might reflect uncontrolled blood pressure levels in humans, we assayed extracellular signal-regulated kinase, c-Jun N-terminal kinase 1, and p38 activation in WBCs isolated from normotensive volunteers, hypertensive patients with controlled blood pressure values, or hypertensive patients with uncontrolled blood pressure values. Interestingly, in hypertensive patients with controlled blood pressure values, LV mass and extracellular signal-regulated kinase phosphorylation were significantly reduced compared with those in hypertensive patients with uncontrolled blood pressure values. These results suggest that MAPKs are sensors of pressure overload and that extracellular signal-regulated kinase activation in WBCs might be used as a novel surrogate biomarker of uncontrolled human hypertension.
Esposito
Giovanni
G
Division of Cardiology, Federico II University, Via Pansini 5, 80131 Naples, Italy. espogiov@unina.it
Perrino
Cinzia
C
Schiattarella
Gabriele Giacomo
GG
Belardo
Lorena
L
di Pietro
Elisa
E
Franzone
Anna
A
Capretti
Giuliana
G
Gargiulo
Giuseppe
G
Pironti
Gianluigi
G
Cannavo
Alessandro
A
Sannino
Anna
A
Izzo
Raffaele
R
Chiariello
Massimo
M
D000818:Animals; D001011:Aorta / Q000503:physiopathology; D009320:Atrial Natriuretic Factor / Q000235:genetics; D001794:Blood Pressure / Q000502:physiology*; D015152:Blotting, Northern; D015153:Blotting, Western; D003251:Constriction, Pathologic; D004789:Enzyme Activation; D005260:Female; D015870:Gene Expression; D006801:Humans; D006973:Hypertension / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology*; D006984:Hypertrophy; D007962:Leukocytes / Q000201:enzymology; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008297:Male; D051379:Mice; D008875:Middle Aged; D019950:Mitogen-Activated Protein Kinase 1 / Q000097:blood / Q000378:metabolism; D048055:Mitogen-Activated Protein Kinase 8 / Q000097:blood / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000097:blood / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D011312:Pressure; D048051:p38 Mitogen-Activated Protein Kinases / Q000097:blood / Q000378:metabolism
D009320:Atrial Natriuretic Factor; D019950:Mitogen-Activated Protein Kinase 1; D048055:Mitogen-Activated Protein Kinase 8; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases