Early left ventricular gene expression profile in response to increase in blood pressure.
The heart adapts to increased pressure overload by hypertrophic growth of terminally differentiated cardiomyocytes. At the genetic level, the hypertrophic response is characterized by the reprogramming of gene expression, i.e. upregulation of immediate early genes, natriuretic peptide genes and genes encoding structural proteins. In the present study, we characterized the early changes in gene expression with cDNA expression arrays in response to increase in blood pressure produced by arginine8-vasopressin infusion (0.05 microg/kg/min, i.v.) for 30 min and 4 h in conscious normotensive rats. Expression profiling revealed differential expression of 14 genes in the left ventricle, and several novel factors of immediate early genetic response to pressure overload were identified, such as growth arrest and DNA damage inducible protein 45 (GADD45alpha), epidermal fatty acid-binding protein (E-FABP) and Bcl-X. Administration of angiotensin II (Ang II) for 6 h by osmotic minipumps also increased left ventricular GADD45alpha, E-FABP and Bcl-X gene expression. Furthermore, the induction of GADD45alpha and Bcl-X gene expression by Ang II was blocked by angiotensin II type 1 receptor antagonist losartan. In summary, our analysis provided new insights into the pathogenesis of pressure overload-induced hypertrophy by suggesting the existence of novel regulators of the immediate early gene expression program.
Rysä
Jaana
J
Department of Pharmacology and Toxicology, Biocenter Oulu, University of Oulu, Finland.
Aro
Jani
J
Ruskoaho
Heikki
H
D000208:Acute Disease; D000804:Angiotensin II / Q000633:toxicity; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use; D001127:Arginine Vasopressin / Q000494:pharmacology / Q000633:toxicity*; D001794:Blood Pressure / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000235:genetics; D002908:Chronic Disease; D003243:Consciousness; D018076:DNA, Complementary / Q000235:genetics; D051766:Early Growth Response Protein 1 / Q000096:biosynthesis / Q000235:genetics; D005136:Eye Proteins / Q000096:biosynthesis / Q000235:genetics; D050556:Fatty Acid-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis / Q000235:genetics; D006352:Heart Ventricles / Q000378:metabolism*; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology; D019808:Losartan / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D020932:Nerve Growth Factor / Q000096:biosynthesis / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D051020:bcl-X Protein / Q000096:biosynthesis* / Q000235:genetics; D000097642:GADD45 Proteins
D000804:Angiotensin II; D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D001127:Arginine Vasopressin; D018797:Cell Cycle Proteins; D018076:DNA, Complementary; D051766:Early Growth Response Protein 1; D005136:Eye Proteins; D050556:Fatty Acid-Binding Proteins; D018840:HSP70 Heat-Shock Proteins; D019808:Losartan; D020932:Nerve Growth Factor; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D051020:bcl-X Protein; C494813:Bcl2l1 protein, rat; C486110:Egr1 protein, rat; C107356:Fabp5 protein, rat; C499073:Gadd45a protein, rat; D000097642:GADD45 Proteins