Dataset Information

Apelin receptor upregulation in spontaneously hypertensive rat contributes to the enhanced vascular smooth muscle cell proliferation by activating autophagy.

ABSTRACT:

Background

Proliferation of vascular smooth muscle cells (VSMCs) plays a vital role in the progression of vascular remodeling and hypertension. Apelin-13 promotes VSMC proliferation of normal rats. This study was designed to investigate the roles of apelin receptor (APJ) and apelin-13 in VSMC proliferation of hypertension rats and underlying mechanisms.

Methods

Primary VSMCs were obtained from aorta of Wistar-Kyoto rat (WKY) and spontaneously hypertensive rat (SHR). The expressions of apelin and APJ were detected by Western bolt and PCR, as well as immunohistochemistry. VSMC proliferation was evaluated with CCK-8 kit, PCNA protein expression and percentage of EdU-positive cells. Autophagy was determined by the ratio of LC3BII to LC3BI, ATG5 and p62 protein expressions, as well as LC3B immunofluorescence.

Results

APJ expression was increased while apelin expression was reduced in aorta and VSMCs of SHR compared with those of WKY. Exogenous apelin-13 promoted VSMC proliferation and autophagy of both WKY and SHR, which were prevented by APJ antagonist F13A. Blockade of APJ had no significant effects on VSMC proliferation and autophagy of WKY, but attenuated VSMC proliferation and autophagy of SHR. Administration of autophagy inhibitor 3-methyladenine (3-MA) not only attenuated VSMC proliferation of SHR, but prevented apelin-13-induced VSMC proliferation of both WKY and SHR.

Conclusions

Apelin-13 stimulates VSMC proliferation via APJ-mediated enhancement in autophagy. APJ upregulation in SHR contributes to the enhanced VSMC proliferation.

SUBMITTER: Xu T

PROVIDER: S-EPMC8106044 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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Publications

Apelin receptor upregulation in spontaneously hypertensive rat contributes to the enhanced vascular smooth muscle cell proliferation by activating autophagy.

Xu Tao T Jia Jian J Xu Na N Ye Chao C Zheng Fen F Yuan Yan Y Zhu Guo-Qing GQ Zhan Yi-Yang YY

Annals of translational medicine 20210401 8

<h4>Background</h4>Proliferation of vascular smooth muscle cells (VSMCs) plays a vital role in the progression of vascular remodeling and hypertension. Apelin-13 promotes VSMC proliferation of normal rats. This study was designed to investigate the roles of apelin receptor (APJ) and apelin-13 in VSMC proliferation of hypertension rats and underlying mechanisms.<h4>Methods</h4>Primary VSMCs were obtained from aorta of Wistar-Kyoto rat (WKY) and spontaneously hypertensive rat (SHR). The expression ...[more]

PMID: 33987325

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Project description:Vascular smooth muscle cell (VSMC) proliferation and apoptosis and the renin-angiotensin system (RAS) play critical roles in the development of essential hypertension. The activation of calcium-sensing receptor (CaSR), functionally expressed in VSMCs, inhibits cyclic adenosine monophosphate (cAMP) formation by elevating intracellular calcium ([Ca2+]i) and then suppressing renin release. The present study aimed to investigate the effects of NPS2143-mediated inhibition of CaSR on VSMC proliferation and apoptosis in spontaneously hypertensive rat (SHR) VSMCs and to assess whether these effects were mediated by alterations to RAS signaling. Primary VSMCs were isolated from the aortas of SHRs and Wistar-Kyoto rats. SHR VSMCs were treated with CaSR antagonist NPS2143 and cell proliferation and CaSR and RAS-related protein expression levels were measured to assess the effect. The results indicated that NPS2143 treatment promoted SHR VSMC proliferation, lower CaSR expression levels and higher RAS-related proteins levels when compared with control treatment. Additional measurement of the expression levels of proteins related to proliferation, remodeling, apoptosis and RAS related proteins, as well as cell viability, cell cycle, cell apoptosis ratio, [Ca2+]i, and the concentration of cAMP was performed after treatment with NPS2143, PLC inhibitor U73122, IP3 receptor antagonist 2-aminoethoxydiphenylborane (APB), adenylyl cyclase-V inhibitor MDL12330A, angiotensin converting enzyme inhibitor captopril, angiotensin I receptor (AT1R) inhibitor losartan, NPS2143 + U73122, NPS2143 + 2-APB, NPS2143 + MDL12330A, NPS2143 + captopril and NPS2143 + losartan. The results suggested that NPS2143 promoted cell proliferation, inhibited cell apoptosis, decreased [Ca2+]i and increased the expression of RAS compared with control treatments. NPS2143 + U73122 and NPS2143 + 2-APB enhanced the effects of NPS2143, while NPS2143 + MDL12330A, NPS2143 + captopril, NPS2143 + losartan attenuated the effected of NPS2143 in SHR VSMCs. Furthermore, the knockdown of AT1R by AT1R-short hairpin RNA also attenuated the effects of NPS2143 compared with NPS2143 alone. Collectively, these data indicated that NPS2143 promoted proliferation and inhibited apoptosis of VSMCs in SHRs, the effect of which was achieved by activation of RAS signaling.

Dataset Information

Apelin receptor upregulation in spontaneously hypertensive rat contributes to the enhanced vascular smooth muscle cell proliferation by activating autophagy.

Background

Methods

Results

Conclusions

Publications

Apelin receptor upregulation in spontaneously hypertensive rat contributes to the enhanced vascular smooth muscle cell proliferation by activating autophagy.

Similar Datasets

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