Proteomic analysis of early left ventricular hypertrophy secondary to hypertension: modulation by antihypertensive therapies.
Untreated or poorly controlled arterial hypertension induced development of pathologic left ventricular hypertrophy (LVH), a common finding in hypertensive patients and a strong predictor of cardiovascular morbidity and mortality. The proteomic approach is a powerful technique to analyze a complex mixture of proteins in various settings. An experimental model of hypertension-induced early LVH was performed in spontaneously hypertensive rats, and the cardiac protein pattern compared with the normotensive Wistar Kyoto counterpart was analyzed. Fifteen altered protein spots were shown in the early stage of LVH. Compared with a previous animal model of established and regressed LVH, three protein spots were common in both models. These three altered protein spots corresponded to two unique proteins that were identified as Calsarcin-1 (CS-1) and ubiquinone biosynthesis protein COQ7 homolog. CS-1 is a negative regulator of the calcineurin/NF-AT pathway. Because upregulation in the expression levels of this protein was observed, the activation level of NF-kappaB by oxidative stress as an alternative pathway was investigated. It was found that antihypertensive therapies partially decreased oxidative stress and normalized the activation of NF-kappaB in the kidneys and aorta NF-kappaB activation but just moderately in the heart. This could be due to the interaction of any specific cardiac protein with any component of the NF-kappaB pathway. In this sense, CS-1 could be a good candidate because it is expressed preferentially in heart, to a lesser extent in smooth muscle cells, but not in kidney. Further investigations are necessary to elucidate the exact role of CS-1 and ubiquinone biosynthesis protein COQ7 in the setting of hypertension-induced LVH.
Gallego-Delgado
Julio
J
Renal and Vascular Pathology Laboratory, Fundación Jiménez Díaz-Universidad Autónoma, Madrid, Spain.
Lazaro
Alberto
A
Osende
Julio I
JI
Esteban
Vanesa
V
Barderas
Maria G
MG
Gomez-Guerrero
Carmen
C
Vega
Ricardo
R
Vivanco
Fernando
F
Egido
Jesus
J
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001011:Aorta / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D006973:Hypertension / Q000150:complications* / Q000188:drug therapy* / Q000473:pathology; D017379:Hypertrophy, Left Ventricular / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D007668:Kidney / Q000378:metabolism; D008297:Male; D008840:Microfilament Proteins; D009124:Muscle Proteins / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D040901:Proteomics; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014451:Ubiquinone / Q000378:metabolism
D000959:Antihypertensive Agents; D002352:Carrier Proteins; D008840:Microfilament Proteins; D009124:Muscle Proteins; C524829:Myoz2 protein, rat; D016328:NF-kappa B; D014451:Ubiquinone; C030777:ubiquinone 7