title: Effects of angiotensin II and insulin on ERK1/2 activation in fibroblasts from hypertensive patients.
abstract: BACKGROUND
  Insulin resistance, a frequent finding in hypertensive patients, leads to accelerated cardiovascular damage. It has been suggested that a crosstalk between angiotensin II and insulin signaling pathways may provoke insulin resistance, and may contribute to the development of cardiovascular damage. To identify a common pathophysiologic pathway between metabolic disorders and cardiovascular remodeling, we investigated the effect of angiotensin II and insulin on extracellular signal regulated kinases 1 and 2 (ERK1/2), isoforms of mitogen-activated protein kinases (MAPK) involved in cellular proliferation and extracellular matrix deposition.
  
  
  METHODS
  Skin fibroblasts from normotensive subjects, insulin sensitive hypertensive subjects, and insulin resistant hypertensive subjects were cultured and used after four passages. The ERK1/2 expression and phosphorylation were measured by Western blot using specific antibodies, respectively anti-ERK1/2 and anti-pERK1/2. Expression of AT1 receptor for angiotensin II was determined by reverse transcriptase-polymerase chain reaction in real time.
  
  
  RESULTS
  The ERK1/2 were similarly expressed in skin fibroblasts from all groups; ERK1/2 phosporylation evoked by angiotensin II was significantly higher in fibroblasts from hypertensive patients in comparison to normotensive subjects, but the increase was observed only in insulin resistant hypertensive subjects. The effect of insulin on ERK1/2 phosphorylation was not significantly different in the three groups. Treatment with the combination of insulin and angiotensin II increased ERK1/2 phosphorylation to a greater extent in comparison to the single agonists in normotensive subjects and in insulin sensitive but not in insulin resistant hypertensive subjects.
  
  
  CONCLUSIONS
  Angiotensin II stimulated ERK1/2 activation is increased in insulin resistant hypertensive subjects, and it may play a role in the pathogenesis of insulin resistance and accelerated cardiovascular damage.
authors.affiliation: Department of Clinical and Experimental Medicine, University of Padova Medical School, Padova, Italy.
authors.forename: Michelangelo
authors.initials: M
authors.lastname: Sartori
authors.forename: Giulio
authors.initials: G
authors.lastname: Ceolotto
authors.forename: Italia
authors.initials: I
authors.lastname: Papparella
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Baritono
authors.forename: Laura
authors.initials: L
authors.lastname: Ciccariello
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Calò
authors.forename: Matteo
authors.initials: M
authors.lastname: Leoni
authors.forename: Andrea
authors.initials: A
authors.lastname: Semplicini
mesh_terms: D000328:Adult; D000804:Angiotensin II / Q000008:administration & dosage / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects*; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D007328:Insulin / Q000008:administration & dosage / Q000627:therapeutic use*; D007333:Insulin Resistance; D007558:Italy; D008297:Male; D008875:Middle Aged; D019950:Mitogen-Activated Protein Kinase 1 / Q000187:drug effects* / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects* / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D010770:Phosphotransferases / Q000187:drug effects / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D015415:Biomarkers; D007004:Hypoglycemic Agents; D007328:Insulin; D044140:Receptor, Angiotensin, Type 1; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D010770:Phosphotransferases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases