Angiotensin II Attenuates the Bioactivities of Human Endothelial Progenitor Cells via Downregulation of β2-Adrenergic Receptor
Cross talks between the renin-angiotensin system (RAS), sympathetic nervous system, and vascular homeostasis are tightly coordinated in hypertension. Angiotensin II (Ang II), a key factor in RAS, when abnormally activated, affects the number and bioactivity of circulating human endothelial progenito...
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| Format: | Article |
| Language: | English |
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Wiley
2018-01-01
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| Series: | Stem Cells International |
| Online Access: | http://dx.doi.org/10.1155/2018/7453161 |
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| author | Seon Jin Lee Da Yeon Kim Jisoo Yun Sung Hyun Choi Seok Yun Jung Songhwa Kang Ji Hye Park Yeon Ju Kim Jong Seong Ha Seung Taek Ji Woong Bi Jang Dong Hyung Lee Dongjun Lee Sang-Mo Kwon |
| author_facet | Seon Jin Lee Da Yeon Kim Jisoo Yun Sung Hyun Choi Seok Yun Jung Songhwa Kang Ji Hye Park Yeon Ju Kim Jong Seong Ha Seung Taek Ji Woong Bi Jang Dong Hyung Lee Dongjun Lee Sang-Mo Kwon |
| author_sort | Seon Jin Lee |
| collection | DOAJ |
| description | Cross talks between the renin-angiotensin system (RAS), sympathetic nervous system, and vascular homeostasis are tightly coordinated in hypertension. Angiotensin II (Ang II), a key factor in RAS, when abnormally activated, affects the number and bioactivity of circulating human endothelial progenitor cells (hEPCs) in hypertensive patients. In this study, we investigated how the augmentation of Ang II regulates adrenergic receptor-mediated signaling and angiogenic bioactivities of hEPCs. Interestingly, the short-term treatment of hEPCs with Ang II drastically attenuated the expression of beta-2 adrenergic receptor (ADRB2), but did not alter the expression of beta-1 adrenergic receptor (ADRB1) and Ang II type 1 receptor (AT1R). EPC functional assay clearly demonstrated that the treatment with ADRB2 agonists significantly increased EPC bioactivities including cell proliferation, migration, and tube formation abilities. However, EPC bioactivities were decreased dramatically when treated with Ang II. Importantly, the attenuation of EPC bioactivities by Ang II was restored by treatment with an AT1R antagonist (telmisartan; TERT). We found that AT1R binds to ADRB2 in physiological conditions, but this binding is significantly decreased in the presence of Ang II. Furthermore, TERT, an Ang II-AT1R interaction blocker, restored the interaction between AT1R and ADRB2, suggesting that Ang II might induce the dysfunction of EPCs via downregulation of ADRB2, and an AT1R blocker could prevent Ang II-mediated ADRB2 depletion in EPCs. Taken together, our report provides novel insights into potential therapeutic approaches for hypertension-related cardiovascular diseases. |
| format | Article |
| id | doaj-art-fec7ecceef264391a141cb1d20fc75cd |
| institution | Kabale University |
| issn | 1687-966X 1687-9678 |
| language | English |
| publishDate | 2018-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Stem Cells International |
| spelling | doaj-art-fec7ecceef264391a141cb1d20fc75cd2025-08-20T03:25:40ZengWileyStem Cells International1687-966X1687-96782018-01-01201810.1155/2018/74531617453161Angiotensin II Attenuates the Bioactivities of Human Endothelial Progenitor Cells via Downregulation of β2-Adrenergic ReceptorSeon Jin Lee0Da Yeon Kim1Jisoo Yun2Sung Hyun Choi3Seok Yun Jung4Songhwa Kang5Ji Hye Park6Yeon Ju Kim7Jong Seong Ha8Seung Taek Ji9Woong Bi Jang10Dong Hyung Lee11Dongjun Lee12Sang-Mo Kwon13Department of Physiology, Laboratory for Vascular Medicine and Stem Cell Biology, Convergence Stem Cell Research Center, Medical Research Institute, Pusan National University School of Medicine, Yangsan 50612, Republic of KoreaDepartment of Physiology, Laboratory for Vascular Medicine and Stem Cell Biology, Convergence Stem Cell Research Center, Medical Research Institute, Pusan National University School of Medicine, Yangsan 50612, Republic of KoreaDepartment of Physiology, Laboratory for Vascular Medicine and Stem Cell Biology, Convergence Stem Cell Research Center, Medical Research Institute, Pusan National University School of Medicine, Yangsan 50612, Republic of KoreaCellular Therapeutics Development Team, Bio Center, Institute of Daewoong Life Science, Department of R&D, Daewoong Pharmaceutical Co., Ltd, Yongin-si, Gyeonggi-do 17028, Republic of KoreaDepartment of Physiology, Laboratory for Vascular Medicine and Stem Cell Biology, Convergence Stem Cell Research Center, Medical Research Institute, Pusan National University School of Medicine, Yangsan 50612, Republic of KoreaDepartment of Physiology, Laboratory for Vascular Medicine and Stem Cell Biology, Convergence Stem Cell Research Center, Medical Research Institute, Pusan National University School of Medicine, Yangsan 50612, Republic of KoreaDepartment of Physiology, Laboratory for Vascular Medicine and Stem Cell Biology, Convergence Stem Cell Research Center, Medical Research Institute, Pusan National University School of Medicine, Yangsan 50612, Republic of KoreaDepartment of Physiology, Laboratory for Vascular Medicine and Stem Cell Biology, Convergence Stem Cell Research Center, Medical Research Institute, Pusan National University School of Medicine, Yangsan 50612, Republic of KoreaDepartment of Physiology, Laboratory for Vascular Medicine and Stem Cell Biology, Convergence Stem Cell Research Center, Medical Research Institute, Pusan National University School of Medicine, Yangsan 50612, Republic of KoreaDepartment of Physiology, Laboratory for Vascular Medicine and Stem Cell Biology, Convergence Stem Cell Research Center, Medical Research Institute, Pusan National University School of Medicine, Yangsan 50612, Republic of KoreaDepartment of Physiology, Laboratory for Vascular Medicine and Stem Cell Biology, Convergence Stem Cell Research Center, Medical Research Institute, Pusan National University School of Medicine, Yangsan 50612, Republic of KoreaDepartment of Obstetrics and Gynecology, Pusan National University, School of Medicine, Busan 50612, Republic of KoreaDepartment of Medical Science, Pusan National University School of Medicine, Yangsan 50612, Republic of KoreaDepartment of Physiology, Laboratory for Vascular Medicine and Stem Cell Biology, Convergence Stem Cell Research Center, Medical Research Institute, Pusan National University School of Medicine, Yangsan 50612, Republic of KoreaCross talks between the renin-angiotensin system (RAS), sympathetic nervous system, and vascular homeostasis are tightly coordinated in hypertension. Angiotensin II (Ang II), a key factor in RAS, when abnormally activated, affects the number and bioactivity of circulating human endothelial progenitor cells (hEPCs) in hypertensive patients. In this study, we investigated how the augmentation of Ang II regulates adrenergic receptor-mediated signaling and angiogenic bioactivities of hEPCs. Interestingly, the short-term treatment of hEPCs with Ang II drastically attenuated the expression of beta-2 adrenergic receptor (ADRB2), but did not alter the expression of beta-1 adrenergic receptor (ADRB1) and Ang II type 1 receptor (AT1R). EPC functional assay clearly demonstrated that the treatment with ADRB2 agonists significantly increased EPC bioactivities including cell proliferation, migration, and tube formation abilities. However, EPC bioactivities were decreased dramatically when treated with Ang II. Importantly, the attenuation of EPC bioactivities by Ang II was restored by treatment with an AT1R antagonist (telmisartan; TERT). We found that AT1R binds to ADRB2 in physiological conditions, but this binding is significantly decreased in the presence of Ang II. Furthermore, TERT, an Ang II-AT1R interaction blocker, restored the interaction between AT1R and ADRB2, suggesting that Ang II might induce the dysfunction of EPCs via downregulation of ADRB2, and an AT1R blocker could prevent Ang II-mediated ADRB2 depletion in EPCs. Taken together, our report provides novel insights into potential therapeutic approaches for hypertension-related cardiovascular diseases.http://dx.doi.org/10.1155/2018/7453161 |
| spellingShingle | Seon Jin Lee Da Yeon Kim Jisoo Yun Sung Hyun Choi Seok Yun Jung Songhwa Kang Ji Hye Park Yeon Ju Kim Jong Seong Ha Seung Taek Ji Woong Bi Jang Dong Hyung Lee Dongjun Lee Sang-Mo Kwon Angiotensin II Attenuates the Bioactivities of Human Endothelial Progenitor Cells via Downregulation of β2-Adrenergic Receptor Stem Cells International |
| title | Angiotensin II Attenuates the Bioactivities of Human Endothelial Progenitor Cells via Downregulation of β2-Adrenergic Receptor |
| title_full | Angiotensin II Attenuates the Bioactivities of Human Endothelial Progenitor Cells via Downregulation of β2-Adrenergic Receptor |
| title_fullStr | Angiotensin II Attenuates the Bioactivities of Human Endothelial Progenitor Cells via Downregulation of β2-Adrenergic Receptor |
| title_full_unstemmed | Angiotensin II Attenuates the Bioactivities of Human Endothelial Progenitor Cells via Downregulation of β2-Adrenergic Receptor |
| title_short | Angiotensin II Attenuates the Bioactivities of Human Endothelial Progenitor Cells via Downregulation of β2-Adrenergic Receptor |
| title_sort | angiotensin ii attenuates the bioactivities of human endothelial progenitor cells via downregulation of β2 adrenergic receptor |
| url | http://dx.doi.org/10.1155/2018/7453161 |
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