Downregulation of Bradykinin Type 2 Receptor Expression in Cardiac Endothelial Cells during Senescence

Laura Nurmi, Hanna M. Heikkilä, Heikki Vapaatalo, Petri T. Kovanen, Ken A. Lindstedt

Tutkimustuotos: ArtikkelijulkaisuArtikkeliTieteellinenvertaisarvioitu

Kuvaus

OBJECTIVES:

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.

METHODS AND 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.
Alkuperäiskielienglanti
LehtiJournal of vascular research : official journal of the European Society of Microcirculation
Vuosikerta49
Numero1
Sivut13-23
Sivumäärä11
ISSN1018-1172
DOI - pysyväislinkit
TilaJulkaistu - 2012
OKM-julkaisutyyppiA1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä, vertaisarvioitu

Tieteenalat

  • 3111 Biolääketieteet

Lainaa tätä

@article{78decfd761f7468e84755482331b79c8,
title = "Downregulation of Bradykinin Type 2 Receptor Expression in Cardiac Endothelial Cells during Senescence",
abstract = "OBJECTIVES: 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.METHODS AND 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.",
keywords = "3111 Biomedicine",
author = "Laura Nurmi and Heikkil{\"a}, {Hanna M.} and Heikki Vapaatalo and Kovanen, {Petri T.} and Lindstedt, {Ken A.}",
year = "2012",
doi = "10.1159/000329615",
language = "English",
volume = "49",
pages = "13--23",
journal = "Journal of vascular research : official journal of the European Society of Microcirculation",
issn = "1018-1172",
publisher = "S.KARGER AG",
number = "1",

}

Downregulation of Bradykinin Type 2 Receptor Expression in Cardiac Endothelial Cells during Senescence. / Nurmi, Laura; Heikkilä, Hanna M. ; Vapaatalo, Heikki; Kovanen, Petri T.; Lindstedt, Ken A.

julkaisussa: Journal of vascular research : official journal of the European Society of Microcirculation, Vuosikerta 49, Nro 1, 2012, s. 13-23.

Tutkimustuotos: ArtikkelijulkaisuArtikkeliTieteellinenvertaisarvioitu

TY - JOUR

T1 - Downregulation of Bradykinin Type 2 Receptor Expression in Cardiac Endothelial Cells during Senescence

AU - Nurmi, Laura

AU - Heikkilä, Hanna M.

AU - Vapaatalo, Heikki

AU - Kovanen, Petri T.

AU - Lindstedt, Ken A.

PY - 2012

Y1 - 2012

N2 - OBJECTIVES: 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.METHODS AND 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.

AB - OBJECTIVES: 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.METHODS AND 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.

KW - 3111 Biomedicine

U2 - 10.1159/000329615

DO - 10.1159/000329615

M3 - Article

VL - 49

SP - 13

EP - 23

JO - Journal of vascular research : official journal of the European Society of Microcirculation

JF - Journal of vascular research : official journal of the European Society of Microcirculation

SN - 1018-1172

IS - 1

ER -