Blood pressure regulates platelet-derived growth factor A-chain gene expression in vascular smooth muscle cells in vivo. An autocrine mechanism promoting hypertensive vascular hypertrophy.
To clarify the role of PDGF A-chain in hypertensive vascular hypertrophy of spontaneously hypertensive rats (SHRs), we studied levels of PDGF A-chain gene expression and transcription factors related to the gene in vascular smooth muscle cells (VSMCs) of SHRs in vivo. RNase protection assay and in situ hybridization showed that PDGF A-chain mRNA levels in VSMCs of SHRs were twofold higher than in those of normotensive Wistar-Kyoto rats. Gel retardation assays showed that levels of Sp1 and AP-2 in VSMCs of SHRs were twofold more abundant than in those of Wistar-Kyoto rats. Treatment with four pharmacologically different species of antihypertensive drugs for 2 wk decreased the levels of both PDGF A-chain mRNA and Sp1, but not AP-2 level in VSMCs of SHRs with regression of aortic hypertrophy, indicating that increases in levels of both PDGF A-chain mRNA and Sp1 in VSMCs of SHRs were associated with high blood pressure. These results suggest that high blood pressure is a stimulus which upregulates PDGF A-chain gene expression in VSMCs of SHRs, resulting in an autocrine enhancement in hypertensive vascular hypertrophy, and that the activation of the gene may be mediated through increases in Sp1 in these cells.
Negoro
N
N
First Department of Internal Medicine, Osaka City University Medical School, Japan.
Kanayama
Y
Y
Haraguchi
M
M
Umetani
N
N
Nishimura
M
M
Konishi
Y
Y
Iwai
J
J
Okamura
M
M
Inoue
T
T
Takeda
T
T
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001011:Aorta / Q000473:pathology; D001483:Base Sequence; D001794:Blood Pressure; D005786:Gene Expression Regulation; D006339:Heart Rate; D006973:Hypertension / Q000150:complications / Q000235:genetics / Q000503:physiopathology*; D006984:Hypertrophy / Q000150:complications; D017403:In Situ Hybridization; D008297:Male; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000473:pathology*; D010982:Platelet-Derived Growth Factor / Q000096:biosynthesis* / Q000235:genetics; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley; D013599:Systole; D014157:Transcription Factors / Q000032:analysis; D017540:Tunica Media / Q000473:pathology
D000959:Antihypertensive Agents; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D014157:Transcription Factors