A proteomic analysis of aorta from spontaneously hypertensive rat: RhoGDI alpha upregulation by angiotensin II via AT(1) receptor.
Arteries undergo remodeling as a consequence of increased wall stress during hypertension. However, the molecular mechanisms of the vascular remodeling are largely unknown. Proteomics is a powerful tool to screen for differentially expressed proteins, but little effort was made on vascular disease research, especially on hypertension. In the present study, the differentially expressed proteins in aortas from 18-week-old spontaneously hypertensive rats (SHR) and their normotensive counterpart, Wistar Kyoto rats (WKY), were examined by two-dimensional electrophoresis (2-DE). We found 50 proteins to be differentially expressed, among which 27 were highly or only expressed in SHR and 23 in WKY. Using matrix-assisted laser desorption/ionisation-time of flight mass spectrometry (MALDI-TOF-MS) and online data search, nine proteins, including Rho GDP dissociation inhibitor alpha (RhoGDIalpha), were identified with high confidence. Further, the upregulation of RhoGDIalpha was verified at both mRNA and protein level in SHR. In addition, when cultured vascular smooth muscle cells (VSMCs) from aortas of SHR and WKY were treated with angiotensin II (Ang II) and antagonist of angiotensin II type I (AT(1)) receptor, L158809, respectively, RhoGDIalpha was upregulated by Ang II and downregulated by L158809 in VSMCs of SHR. These results demonstrate that vascular remodeling results in significant alterations in the protein expression profile of the aorta during hypertension and suggest that the upregulation of RhoGDIalpha in hypertension is induced by Ang II via AT(1) receptor.
Bian
Yu-Lan
YL
Institute of Mechanobiology and Medical Engineering, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Minhang, Shanghai , China.
Qi
Yin-Xin
YX
Yan
Zhi-Qiang
ZQ
Long
Ding-Kun
DK
Shen
Bao-Rong
BR
Jiang
Zong-Lai
ZL
D000804:Angiotensin II / Q000494:pharmacology; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000378:metabolism*; D020730:Guanine Nucleotide Dissociation Inhibitors / Q000235:genetics / Q000378:metabolism*; D006973:Hypertension / Q000378:metabolism*; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D040901:Proteomics / Q000379:methods; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013777:Tetrazoles / Q000494:pharmacology; D015854:Up-Regulation; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D062947:rho-Specific Guanine Nucleotide Dissociation Inhibitors
D047228:Angiotensin II Type 1 Receptor Blockers; D020730:Guanine Nucleotide Dissociation Inhibitors; D007093:Imidazoles; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles; D014662:Vasoconstrictor Agents; D062947:rho-Specific Guanine Nucleotide Dissociation Inhibitors; D000804:Angiotensin II; C070967:L 158809