PMID- 19901160 OWN - NLM STAT- MEDLINE DCOM- 20100121 LR - 20160726 IS - 1524-4563 (Electronic) IS - 0194-911X (Linking) VI - 55 IP - 1 DP - 2010 Jan TI - Induction of mitogen-activated protein kinases is proportional to the amount of pressure overload. PG - 137-43 LID - 10.1161/HYPERTENSIONAHA.109.135467 [doi] AB - 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. FAU - Esposito, Giovanni AU - Esposito G AD - Division of Cardiology, Federico II University, Via Pansini 5, 80131 Naples, Italy. espogiov@unina.it FAU - Perrino, Cinzia AU - Perrino C FAU - Schiattarella, Gabriele Giacomo AU - Schiattarella GG FAU - Belardo, Lorena AU - Belardo L FAU - di Pietro, Elisa AU - di Pietro E FAU - Franzone, Anna AU - Franzone A FAU - Capretti, Giuliana AU - Capretti G FAU - Gargiulo, Giuseppe AU - Gargiulo G FAU - Pironti, Gianluigi AU - Pironti G FAU - Cannavo, Alessandro AU - Cannavo A FAU - Sannino, Anna AU - Sannino A FAU - Izzo, Raffaele AU - Izzo R FAU - Chiariello, Massimo AU - Chiariello M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20091109 PL - United States TA - Hypertension JT - Hypertension (Dallas, Tex. : 1979) JID - 7906255 RN - 85637-73-6 (Atrial Natriuretic Factor) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 8) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) SB - IM CIN - Hypertension. 2010 Jan;55(1):23-5. PMID: 19901156 MH - Animals MH - Aorta/physiopathology MH - Atrial Natriuretic Factor/genetics MH - Blood Pressure/*physiology MH - Blotting, Northern MH - Blotting, Western MH - Constriction, Pathologic MH - Enzyme Activation MH - Female MH - Gene Expression MH - Humans MH - Hypertension/enzymology/genetics/*physiopathology MH - Hypertrophy MH - Leukocytes/enzymology MH - MAP Kinase Signaling System/*physiology MH - Male MH - Mice MH - Middle Aged MH - Mitogen-Activated Protein Kinase 1/blood/metabolism MH - Mitogen-Activated Protein Kinase 8/blood/metabolism MH - Mitogen-Activated Protein Kinases/blood/*metabolism MH - Myocardium/metabolism/pathology MH - Phosphorylation MH - Pressure MH - p38 Mitogen-Activated Protein Kinases/blood/metabolism EDAT- 2009/11/11 06:00 MHDA- 2010/01/22 06:00 CRDT- 2009/11/11 06:00 PHST- 2009/11/11 06:00 [entrez] PHST- 2009/11/11 06:00 [pubmed] PHST- 2010/01/22 06:00 [medline] AID - HYPERTENSIONAHA.109.135467 [pii] AID - 10.1161/HYPERTENSIONAHA.109.135467 [doi] PST - ppublish SO - Hypertension. 2010 Jan;55(1):137-43. doi: 10.1161/HYPERTENSIONAHA.109.135467. Epub 2009 Nov 9.