Human cytomegalovirus induces upregulation of arginase II possible implications for vasculopathies
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Human cytomegalovirus induces upregulation of arginase II possible implications for vasculopathies. / Yaiw, Koon-Chu; Mohammad, Abdul-Aleem; Taher, Chato; Wilhelmi, Vanessa; Davoudi, Belghis; Strååt, Klas; Assinger, Alice; Ovchinnikova, Olga; Shlyakhto, Eugene; Rahbar, Afsar; Koutonguk, Oksana; Religa, Piotr; Butler, Lynn; Khan, Zahidul; Streblow, Daniel; Pernow, John; Söderberg-Nauclér, Cecilia.
in: BASIC RES CARDIOL, Jahrgang 109, Nr. 2, 01.03.2014, S. 401.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - Human cytomegalovirus induces upregulation of arginase II possible implications for vasculopathies
AU - Yaiw, Koon-Chu
AU - Mohammad, Abdul-Aleem
AU - Taher, Chato
AU - Wilhelmi, Vanessa
AU - Davoudi, Belghis
AU - Strååt, Klas
AU - Assinger, Alice
AU - Ovchinnikova, Olga
AU - Shlyakhto, Eugene
AU - Rahbar, Afsar
AU - Koutonguk, Oksana
AU - Religa, Piotr
AU - Butler, Lynn
AU - Khan, Zahidul
AU - Streblow, Daniel
AU - Pernow, John
AU - Söderberg-Nauclér, Cecilia
PY - 2014/3/1
Y1 - 2014/3/1
N2 - Both human cytomegalovirus (HCMV) and arginase II (ARG II) have been implicated in the pathogenesis of cardiovascular diseases. The effects of HCMV on ARG II are unknown. The aim of this study was to investigate the effects of HCMV on ARG II expression in endothelial and vascular smooth muscle cells (SMC) both in vitro and ex vivo. Endothelial and SMC were infected with either HCMV or UV-irradiated HCMV. Expression of ARG II, endothelial or inducible nitric oxide synthase (eNOS and iNOS, respectively) and viral immediate early (IE) was quantified using quantitative PCR. Ganciclovir and short interfering RNA were used to determine the viral gene mediating the effects on ARG II. Detection of viral antigens and ARG II expression was performed by immunofluorescence or immunohistochemistry. HCMV infection increased both ARG II mRNA and protein levels in the examined cells; this effect was mediated by the HCMV IE2-p86 protein. The upregulation of ARG II was accompanied by a downregulation of eNOS but an induction of iNOS in HCMV-infected endothelial cells. Both eNOS and iNOS expressions were induced in HCMV-infected SMC. ARG II was abundantly expressed in endothelial cells, foam cells and SMC and was importantly significantly upregulated in HCMV-immunoreactive human carotid atherosclerotic plaques. HCMV IE2-p86 mediates ARG II upregulation in vitro and ARG II is co-expressed with HCMV antigens in human carotid atherosclerotic plaques. We speculate that HCMV may contribute to endothelial dysfunction via ARG II induction and reduced eNOS production.
AB - Both human cytomegalovirus (HCMV) and arginase II (ARG II) have been implicated in the pathogenesis of cardiovascular diseases. The effects of HCMV on ARG II are unknown. The aim of this study was to investigate the effects of HCMV on ARG II expression in endothelial and vascular smooth muscle cells (SMC) both in vitro and ex vivo. Endothelial and SMC were infected with either HCMV or UV-irradiated HCMV. Expression of ARG II, endothelial or inducible nitric oxide synthase (eNOS and iNOS, respectively) and viral immediate early (IE) was quantified using quantitative PCR. Ganciclovir and short interfering RNA were used to determine the viral gene mediating the effects on ARG II. Detection of viral antigens and ARG II expression was performed by immunofluorescence or immunohistochemistry. HCMV infection increased both ARG II mRNA and protein levels in the examined cells; this effect was mediated by the HCMV IE2-p86 protein. The upregulation of ARG II was accompanied by a downregulation of eNOS but an induction of iNOS in HCMV-infected endothelial cells. Both eNOS and iNOS expressions were induced in HCMV-infected SMC. ARG II was abundantly expressed in endothelial cells, foam cells and SMC and was importantly significantly upregulated in HCMV-immunoreactive human carotid atherosclerotic plaques. HCMV IE2-p86 mediates ARG II upregulation in vitro and ARG II is co-expressed with HCMV antigens in human carotid atherosclerotic plaques. We speculate that HCMV may contribute to endothelial dysfunction via ARG II induction and reduced eNOS production.
KW - Antiviral Agents
KW - Aorta
KW - Arginase
KW - Carotid Artery Diseases
KW - Cytomegalovirus
KW - Cytomegalovirus Infections
KW - Endothelial Cells
KW - Ganciclovir
KW - Gene Expression Regulation, Enzymologic
KW - Gene Expression Regulation, Viral
KW - Human Umbilical Vein Endothelial Cells
KW - Humans
KW - Immediate-Early Proteins
KW - Muscle, Smooth, Vascular
KW - Nitric Oxide Synthase Type II
KW - Nitric Oxide Synthase Type III
KW - Pulmonary Artery
KW - RNA, Messenger
KW - RNA, Small Interfering
KW - Trans-Activators
KW - Up-Regulation
KW - Vasculitis
U2 - 10.1007/s00395-014-0401-5
DO - 10.1007/s00395-014-0401-5
M3 - SCORING: Journal article
C2 - 24442486
VL - 109
SP - 401
JO - BASIC RES CARDIOL
JF - BASIC RES CARDIOL
SN - 0300-8428
IS - 2
ER -