Elevated mineralocorticoid receptor activity in aged rat vascular smooth muscle cells promotes a proinflammatory phenotype via extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase and epidermal growth factor receptor-dependent pathways

Alexander W. Krug, Lena Allenhöfer, Robert Monticone, Gaia Spinetti, Michael Gekle, Mingyi Wang, Edward G. Lakatta

Research output: Contribution to journalArticlepeer-review

Abstract

Arterial aging is a predominant risk factor for the onset of cardiovascular diseases, such as hypertension, myocardial infarction, or stroke. Aging is associated with intravascular renin-angiotensin system activation, increased vascular stiffness, intima-media thickening, and a proinflammatory phenotype. Little is known about the influence of aldosterone on arterial aging. Hence, we hypothesized that aldosterone and mineralocorticoid receptor (MR) activation might contribute to and possibly accelerate the arterial aging process. We demonstrate increased MR expression in whole aortae and early passage aortic vascular smooth muscle cells from aged (30 months) compared with adult (8 months) F344XBN rats. Sensitivity to aldosterone-induced extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase activity is increased in aged cells. MR blockade and extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase inhibition prevent age-associated increases of transforming growth factor-β, intercellular adhesion molecule 1, and procollagen 1. Aldosterone increases expression of proinflammatory marker proteins, shifting the phenotype of adult vascular smooth muscle cells toward the proinflammatory phenotype of aged rats. Epidermal growth factor receptor expression is increased with age and by aldosterone, and inhibition of epidermal growth factor receptor tyrosine kinase decreases age-associated proinflammatory marker expression. Our data support the hypothesis that increased constitutive MR signaling may promote and amplify age-associated inflammation that accompanies arterial aging through increased angiotensin II-stimulated expression of MR and enhanced sensitivity to aldosterone-mediated extracellular signal-regulated kinase 1/2 activation, likely related to increased epidermal growth factor receptor expression.

Original languageEnglish (US)
Pages (from-to)1476-1483
Number of pages8
JournalHypertension
Volume55
Issue number6
DOIs
StatePublished - Jun 2010
Externally publishedYes

Keywords

  • Aldosterone
  • Arterial aging
  • Inflammation
  • Mineralocorticoid receptor
  • Vascular smooth muscle cells

ASJC Scopus subject areas

  • Internal Medicine

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