Effects of hypertension and aging on platelet-derived growth factor and platelet-derived growth factor receptor expression in rat aorta and heart.

Abstract

Previous investigations have demonstrated certain similarities in the cellular changes occurring in the arterial wall in response to hypertension and aging. We undertook the current studies to examine the expression of platelet-derived growth factor (PDGF) receptors and ligands and transforming growth factor-beta 1 (TGF-beta 1) in aorta and heart of spontaneously hypertensive rats (SHRs), Wistar-Kyoto (WKY) controls, and Wistar rats studied at ages ranging from 5 to 40 weeks. A progressive increase with age in aortic steady-state messenger RNA (mRNA) levels of the receptor for the B chain of PDGF (PDGF-r beta) was present in all three strains but was greatest in the SHR. The aortic expression of PDGF A or B ligands as well as of the PDGF-r alpha-receptor was not significantly influenced by age or blood pressure. In contrast, in the heart of the SHR and WKY rat, there was an age-related decrease in expression of both PDGF receptors and of the PDGF B chain. Hypertension and aging were associated with increases in steady-state mRNA for TGF-beta 1 in aorta, but in the heart, reductions again were observed. These studies indicate that both hypertension and aging increase the in vivo expression of PDGF-r beta and TGF-beta 1 in aortic tissue. Such changes might be functionally significant and provide autocrine or paracrine mechanisms for regulation of cellular growth in the arterial wall in response to these conditions. The findings also provide further support for the concept that hypertension accelerates the arterial changes associated with aging.

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.

“…However, these findings differ significantly from the results of Sarzani et al (42,43) who reported that PDGF A-chain mRNA levels in rat aortas were too low to study between strains. Although the reason for this difference is unclear, it is possible that (a) the sensitivities of the assays in the former studies including ours were higher than that of Sarzani et al, and (b) the samples used by Sarzani et al may have been contaminated with adventitial tissue because their samples contained PDGF B-chain mRNA, which is never expressed in VSMCs, but is strongly expressed in aortic adventitial tissue ( 14).…”

Platelet-Derived Growth Factor-AB Limits the Extent of Myocardial Infarction in a Rat Model

“…PDGF-B expression, however, was detected only in young adult murine cardiac samples, which is in agreement with previous findings in the rat heart. 17 Furthermore, transwell cocultures confirmed that CMECs of both young and senescent hearts constitutively expressed PDGF-A ( Figure 1B and 1C). However, only the young adult CMECs expressed PDGF-B in the presence of the fetal cardiac myocytes, resulting in a significant increase in protein levels of PDGF-B in the CMECs of the 3-but not the 18-month-old hearts.…”

“…This results in the induction of a cascade of molecular events that maintain vascular integrity, including the endothelial expression of vascular endothelial growth factor (VEGF) and VEGF receptor-2 (Flk-1, VEGFR-2). Therefore, dysregulation of these angiogenic pathways, which occurs in aging through alterations in cardiac PDGFlevels, 17 may lead to angiogenic defects. On the basis of these previous observations, we hypothesized that interventions targeted at reestablishing the angiogenic potential in senescent cardiac endothelial function may attenuate the detrimental impact of obstructive vascular disease in the aging heart.…”

Transforming growth factor-beta 1 gene activation and growth of smooth muscle from hypertensive rats.

“…Others have shown increased expression of TGF-/31 mRNA levels in the aorta of SHR and WKY rats as their age increases from 5 to 40 weeks. 15 Elevated mRNA levels encoding TGF-/31 have also been reported in VSMC from SHR, compared with those from WKY rats, cultured in the presence of serum. 16 More recently it has been suggested that increased TGF-/31 expression and activation is associated with augmented proliferation of VSMC from SHR.…”