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.

Negoro, Nobuo; Kanayama, Yoshiharu; Haraguchi, Misa; N, Umetani; Nishimura, M; Konishi, Yoshio; Iwai, Junko; Okamura, Mitsu; Inoue, Takatoshi; Takeda, Tadanao

doi:10.1172/jci117762

Cited by 56 publications

(28 citation statements)

References 47 publications

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“…Previous work from this laboratory showed that PDGF-A expression and vascular wall hypertrophy both correlate with blood pressure in the 1K1C hypertensive rat (6). Decreasing blood pressure by different antihypertensive agents in the SHR also produced a decrease in PDGF-A expression and aortic hypertrophy, both of which correlated with the change in blood pressure (29). These results from two different models of hypertension suggest that pressure mediates PDGF-A expression in the arterial VSMCs.…”

Section: Discussionmentioning

confidence: 52%

AT₁ receptor inhibition does not reduce arterial wall hypertrophy or PDGF-A expression in renal hypertension

Parker

Dobrian

Wade

et al. 2000

American Journal of Physiology-Heart and Circulatory Physiology

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. AT 1 receptor inhibition does not reduce arterial wall hypertrophy or PDGF-A expression in renal hypertension. Am. J. Physiol. Heart Circ. Physiol. 278: H613-H622, 2000.-To separate the role of ANG II from pressure in hypertrophy of the vascular wall in one-kidney, one-clip (1K1C) hypertension, experimental and shamoperated rats were given the AT 1 -receptor antagonist losartan (20 mg · kg Ϫ1 · day Ϫ1 ) or tap water for 14 days. Mean arterial pressure was elevated in both experimental groups compared with controls. Rats were anesthetized with pentobarbital sodium, and the thoracic aorta and carotid, small mesenteric, and external spermatic arteries were harvested and embedded in paraffin. Tissue sections were used for morphological analysis, immunohistochemistry for 5-bromo-2Ј-deoxyuridine (BrdU) and platelet-derived growth factor (PDGF)-AA, stereological measurements, and in situ hybridization with a 35 S-labeled riboprobe for PDGF-A mRNA. Elevated cross-sectional areas of thoracic, carotid, and small mesenteric artery in 1K1C rats were not reduced by losartan. The internal diameter of the external spermatic artery and microvascular density of the cremaster muscle were reduced in 1K1C rats. The number of BrdU-positive nuclei per cross section did not differ between 1K1C and control arteries. PDGF-A mRNA was elevated in the arterial walls of 1K1C rats compared with controls and was hardly changed by losartan. PDGF-A protein stained strongly in the media of 1K1C arteries and was not inhibited by losartan; it appeared in the adventitia of all aortas and carotid arteries. These observations demonstrate that effects of ANG II mediated through the AT 1 receptor are not necessary for hypertrophy of the vascular wall during 1K1C hypertension or expression of PDGF-A.one-kidney, one-clip hypertension; losartan; arterial pressure; angiotensin; platelet-derived growth factor DURING THE COURSE of hypertension, individual arteries adapt to mechanical and hormonal stresses through alterations in medial thickness and/or internal and external diameters, depending on the size and function of the particular blood vessel. The larger arteries increase wall cross-sectional area with the development of outward hypertrophy (30, 45). The smaller arterioles undergo a decrease in lumen size without an increase in wall area and/or rarefaction, the reduction in number of functional vessels (16,31,38). Lumen reduction in the absence of hypertrophy is termed ''inward, eutrophic remodeling.'' Both ANG II and pressure have been implicated as stimuli for the vascular changes associated with hypertension (4,9,18,30,45). ANG II is a hypertrophic (18) as well as hyperplastic stimulus (47) of vascular smooth muscle cells (VSMCs) and has been shown to induce platelet-derived growth factor (PDGF)-A chain expression (28). Recently, we have shown that vascular hypertrophy following chronic infusion of ANG II was entirely prevented when the blood pressure was kept from rising by the simultaneous administration of minoxidil (34). Pressure, like ANG II,...

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Section: Discussionmentioning

confidence: 52%

AT₁ receptor inhibition does not reduce arterial wall hypertrophy or PDGF-A expression in renal hypertension

Parker

Dobrian

Wade

et al. 2000

American Journal of Physiology-Heart and Circulatory Physiology

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“…The transcription factor Sp1 positively regulates target gene expression upon BP rise in vascular smooth muscle cells. 32 After the demethylation of H3K27me3, Sp1 that is recruited to the promoter may lead to positive regulation of the Nkcc1 gene with co-activators such as histone acetyltransferases in hypertensive rats. Although Ang II increased the histone acetylation for IGF-IIreceptor gene expression, 33 it is still not clear whether the upregulation of the Nkcc1 gene promoter activity is caused by indirect mechanisms downstream of Ang II, such as oxidative stress and high BP, or by a direct mechanism through the activation of Ang II receptors.…”

Section: Discussionmentioning

confidence: 99%

Upregulation of the Na+-K+-2Cl− cotransporter 1 via histone modification in the aortas of angiotensin II-induced hypertensive rats

et al. 2012

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The Na þ -K þ -2Cl À cotransporter 1 (NKCC1) is upregulated in diverse models of hypertension. We hypothesized that NKCC1 is upregulated via histone modification in the aortas of angiotensin II (Ang II)-induced hypertensive rats. An osmotic mini-pump containing Ang II was implanted in the subcutaneous tissues of the backs of Sprague-Dawley (SD) rats for 7 days. The systolic blood pressure was recorded every day by the tail-cuff method. On days 3 and 7, the mesenteric arteries were excised, cut into rings, mounted in organ baths and subjected to vascular contraction. The levels of Nkcc1 mRNA and protein in the aortas were measured using real-time PCR and Western blotting, respectively. The histone modifications and recruited proteins at the Nkcc1 promoter were determined by chromatin immunoprecipitation. The inhibition of concentration-response curves to phenylephrine by bumetanide, an inhibitor of NKCCs, was greater in Ang II-infused rats than in sham-operated (sham) rats . The levels of Nkcc1 mRNA and protein in the aortas increased gradually as Ang II was infused into the rats. Acetylated histone H3 (H3Ac), an activating histone code, was increased but trimethylated histone H3 at lysine 27 (H3K27me3), a repressive histone code, was greatly decreased in Ang II-infused rats compared with sham. RNA polymerase II was recruited to the Nkcc1 promoter with increased KDM6b. We conclude that the NKCC1 is upregulated via histone modification in the aortas of Ang II-induced hypertensive rats. Thus, we suggest that this ion transporter is epigenetically upregulated by histone modification or DNA demethylation upon the development of hypertension.

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“…Several studies have emphasized the role that PDGF-A may play in the remodeling of the arterial wall in hypertension. Increased PDGF-A expression has been found in aortas of spontaneously hypertensive rats (SHR) and angiotensin-treated rats (26,42). Moreover, the treatment of SHR with antisense oligonucleotides for PDGF-A significantly reduced hypertrophy of the thoracic aorta, without altering blood pressure (11).…”

Section: Discussionmentioning

confidence: 99%

“…Also, smooth muscle cells isolated from thoracic aortas of newborn and adult rats constitutively express PDGF-A message (33,36). There are data showing enhanced expression of PDGF-A chain mRNA in thoracic aorta of spontaneously hypertensive rats (26), hypertensive Sprague-Dawley rats (23), and angiotensin-treated Wistar rats (42).…”

mentioning

confidence: 99%

PDGF-A expression correlates with blood pressure and remodeling in 1K1C hypertensive rat arteries

Dobrian

Wade

Prewitt

1999

American Journal of Physiology-Heart and Circulatory Physiology

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Dobrian, Anca, Suzanne S. Wade, and Russell L. Prewitt. PDGF-A expression correlates with blood pressure and remodeling in 1K1C hypertensive rat arteries. Am. J. Physiol. 276 (Heart Circ. Physiol. 45): H2159-H2167, 1999.-We previously demonstrated remodeling of large and small arteries in angiotensin II-treated rats, paralleled by an increased expression of platelet-derived growth factor (PDGF)-A chain mRNA in large arteries. Both remodeling and PDGF-A expression were associated with elevation of blood pressure rather than a direct effect of angiotensin II. To further delineate the role of PDGF-A and elevated blood pressure, we assessed the level of PDGF-A and -B mRNA and protein in the wall of large as well as small arteries in the one-kidney, one-clip (1K1C) hypertensive rat, a non-renindependent model of hypertension. Fourteen days after renal artery stenosis, the thoracic aorta and both femoral arteries were collected from 1K1C rats (n ϭ 8) and uninephrectomized controls (n ϭ 8) and immediately processed for morphological measurement, immunohistochemistry, RT-PCR, and Western blotting. Systolic blood pressure was significantly elevated in hypertensive rats (202 Ϯ 26 mmHg) compared with control rats (122 Ϯ 7.9 mmHg) and was accompanied by arterial hypertrophy in both aorta and femoral arteries. The mRNA for PDGF-A chain was increased threefold in the thoracic aorta (P Ͻ 0.05) of 1K1C rats, whereas the message for PDGF-B was not significantly changed in hypertensive versus control animals. A higher staining of the intima-media was observed by using an anti-PDGF-A chain polyclonal antibody on paraffin-embedded sections. Western blot results indicated an ϳ2-fold increase in PDGF-A protein in aortic and femoral wall of the 1K1C rats. The results showed that both the mRNA and protein for PDGF-A chain are increased and well correlated with the blood pressure and wall area, suggesting a direct effect of elevated pressure on PDGF synthesis, which, in turn, may affect the onset and progression of vascular hypertrophy. hypertension; aorta; femoral artery; platelet-derived growth factors; hypertrophy HYPERTENSION IS ACCOMPANIED by vascular changes that vary according to the size and structure of each particular artery. These changes include the hypertrophy of large arteries (27, 41) and the inward eutrophic remodeling of arterioles (13, 28), whereas small arteries (internal diameter 150-250 µm) may undergo inward eutrophic or hypertrophic remodeling, depending on the type of hypertension (12, 16). The exact mechanisms and the factors affecting these vascular changes are only known in part. Lately, the involvement of growth factors in the processes of vascular growth and remodeling has been emphasized. Among them, plateletderived growth factor (PDGF) is of special interest for the autocrine regulation of protein synthesis (9) and growth (7) in smooth muscle cells. Large vessels from normotensive rats and humans constitutively express low levels of PDGF-A mRNA, mainly in the medial layer, whereas the PDGF-B chain mRNA is ...

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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.

Cited by 56 publications

References 47 publications

AT₁ receptor inhibition does not reduce arterial wall hypertrophy or PDGF-A expression in renal hypertension

AT₁ receptor inhibition does not reduce arterial wall hypertrophy or PDGF-A expression in renal hypertension

Upregulation of the Na+-K+-2Cl− cotransporter 1 via histone modification in the aortas of angiotensin II-induced hypertensive rats

PDGF-A expression correlates with blood pressure and remodeling in 1K1C hypertensive rat arteries

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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.

Cited by 56 publications

References 47 publications

AT1 receptor inhibition does not reduce arterial wall hypertrophy or PDGF-A expression in renal hypertension

AT1 receptor inhibition does not reduce arterial wall hypertrophy or PDGF-A expression in renal hypertension

Upregulation of the Na+-K+-2Cl− cotransporter 1 via histone modification in the aortas of angiotensin II-induced hypertensive rats

PDGF-A expression correlates with blood pressure and remodeling in 1K1C hypertensive rat arteries

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AT₁ receptor inhibition does not reduce arterial wall hypertrophy or PDGF-A expression in renal hypertension

AT₁ receptor inhibition does not reduce arterial wall hypertrophy or PDGF-A expression in renal hypertension