title: Induction of mitogen-activated protein kinases is proportional to the amount of pressure overload.
abstract: 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.
authors.affiliation: Division of Cardiology, Federico II University, Via Pansini 5, 80131 Naples, Italy. espogiov@unina.it
authors.forename: Giovanni
authors.initials: G
authors.lastname: Esposito
authors.forename: Cinzia
authors.initials: C
authors.lastname: Perrino
authors.forename: Gabriele Giacomo
authors.initials: GG
authors.lastname: Schiattarella
authors.forename: Lorena
authors.initials: L
authors.lastname: Belardo
authors.forename: Elisa
authors.initials: E
authors.lastname: di Pietro
authors.forename: Anna
authors.initials: A
authors.lastname: Franzone
authors.forename: Giuliana
authors.initials: G
authors.lastname: Capretti
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Gargiulo
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Pironti
authors.forename: Alessandro
authors.initials: A
authors.lastname: Cannavo
authors.forename: Anna
authors.initials: A
authors.lastname: Sannino
authors.forename: Raffaele
authors.initials: R
authors.lastname: Izzo
authors.forename: Massimo
authors.initials: M
authors.lastname: Chiariello
mesh_terms: 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
chemical_list: 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