title: Downregulation of Bradykinin type 2 receptor expression in cardiac endothelial cells during senescence.
abstract: OBJECTIVE
  Bradykinin type 2 receptor (BK-2R) knockout mice develop microvascular dysfunction and cardiac hypertrophy. In aged human cardiac microvascular endothelium, dysfunction develops before heart failure symptoms. Since endothelial aging is an independent risk factor for cardiovascular disease, we aimed to clarify the role of kinin receptors in age-related endothelial senescence.
  
  
  RESULTS
  Using qRT-PCR, a downregulation of BK-2Rs during senescence of cultured human coronary artery endothelial cells (HCAECs) and rat cardiac microvascular endothelial cells (RCMECs) was observed. BK-2R downregulation was associated with a decreased cell proliferation rate, with a growth arrest phenotype and reduced angiogenic potential. By staining senescence-associated β-galactosidase, RCMECs from old spontaneously hypertensive rats (SHRs) were found to be significantly more senescent than those derived from age-matched WKY rats, albeit their telomere lengths were similar. Despite downregulation of BK-2Rs and BK-1Rs, a novel family member GPR-100 was highly expressed in HCAECs throughout the culture period.
  
  
  CONCLUSIONS
  Aging cardiac endothelial cells gradually lose their capacity to express BK-2Rs, and this loss appears to be parallel with a loss of the angiogenic potential of the aging cells. Since RCMECs from hypertensive rats showed premature senescence, hypertension may predispose to cardiac dysfunction by accelerating endothelial aging.
authors: Wihuri Research Institute, University of Helsinki, Finland. lrnurmi@gmail.com
authors: Laura
authors: L
authors: Nurmi
authors: Hanna M
authors: HM
authors: Heikkilä
authors: Heikki
authors: H
authors: Vapaatalo
authors: Petri T
authors: PT
authors: Kovanen
authors: Ken A
authors: KA
authors: Lindstedt
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000502:physiology*; D015536:Down-Regulation; D042783:Endothelial Cells / Q000502:physiology*; D006801:Humans; D006973:Hypertension / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D018919:Neovascularization, Physiologic; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017208:Rats, Wistar; D043782:Receptor, Bradykinin B2 / Q000235:genetics / Q000502:physiology*
chemical_list: D043782:Receptor, Bradykinin B2