Angiotensin II-stimulated protein synthesis in cultured vascular smooth muscle cells.

Abstract

To investigate the role of vasoconstrictor hormones in vascular smooth muscle cell growth we have studied the effects of the potent vasoconstrictor angiotensin II on cell growth in a cultured rat aortic cell model. Angiotensin II was not mitogenic for these cells, as assessed by determining cell number, nor was it synergistic in this regard with 10% calf serum. However, 24-hour exposure to 100 nM angiotensin II caused an 80% increase in protein synthesis (compared with 0.4% increase with serum control) as measured by tritiated leucine incorporation. This was a "hypertrophic" response as indicated by a 30% increase in protein content and a 45% increase in cell volume. Angiotensin O-induced smooth muscle cell hypertrophy was maximal at 100 nM, had In hypertensive models such as aortic coarctation and experimental injury models of atherosclerosis, VSMC migration into and proliferation (hyperplasia) in the intima is the most dramatic pathological feature. Received March 28, 1988; accepted November 18, 1988. 107-111-day-old SHR that VSMC proliferation rather than hypertrophy or hyperploidy appeared to account for the increase in VSMC mass. Several factors have been implicated in growth of VSMC in these models. In experimental injury models, endothelial dysfunction or denudation may result in abnormal interactions between elements in the blood (platelets, polymorphonuclear leukocytes, and monocytes) and the vessel wall that lead to sustained release of a variety of growth factors including platelet-derived growth factor. These growth factors are both chemotactic and mitogenic for VSMC 67 and thus may contribute to VSMC migration and proliferation in this model. In certain hypertensive models the increased blood pressure may result in altered mechanical stress that stimulates VSMC growth in a manner analogous to the effects of stretch on skeletal muscle protein synthesis.8 This explanation is supported by data that demonstrate a significant correlation between blood pressure and aortic VSMC hypertrophy and polyploidy. 6 -7 Furthermore, reduction of blood pressure in the SHR model can decrease VSMC polyploidy and hypertrophy.

Leucocyte Na+/H+ antiport activity in Type 1 (insulin-dependent) diabetic patients with nephropathy

“…This increased wall to lumen ratio could itself sustain hypertension [33]. Vascular agonists such as angiotensin II and catecholamines and growth factors such as epidermal growth factor and platelet derived growth factor could not only stimulate Na+/H + antiport activity but also act as trophic stimuli for vascular smooth muscle cells [34,35]. Further support for this notion comes from the increased smooth muscle cellular proliferation when cells are isolated from blood vessels of spontaneously hypertensive rats [37] and increased thymidine incorporation in blood vessels in vivo even in the pre-hypertensive stage [38].…”

Angiotensin II Stimulates Phosphorylation of the Translational Repressor 4E-binding Protein 1 by a Mitogen-activated Protein Kinase-independent Mechanism

“…The increased synthesis of proteins like ␣-actin, collagen, or thrombospondin is accompanied by a corresponding increase in their specific mRNAs, which is indicative of the importance of transcriptional control in the overall stimulation of protein synthesis (6 -9). In agreement with this notion, the transcriptional inhibitor actinomycin D can prevent AII-induced accumulation of proteins in chronically stimulated vascular SMC (2). 2 On the other hand, the global nature of the trophic effect of AII suggests that regulatory changes at the translational level are likely to be involved in the hormone response.…”

“…The peptide hormone angiotensin II (AII) 1 potently stimulates protein synthesis and induces cellular hypertrophy in cultured rat vascular SMC (1)(2)(3)(4). This growth-promoting effect is mediated by the AT 1 receptor subtype, a member of the G protein-coupled receptors superfamily (4,5).…”

Genes and the ageing muscle: a review on genetic association studies

“…The D and I alleles are usually associated with higher and lower ACE enzyme activity respectively (Danser et al 1995;Tiret et al 1992;Williams et al 2005). The primary role of ACE in the renin-angiotensin system is to convert angiotensin I into angiotensin II (Rigat et al 1990), which not only acts as a vasoconstrictor but also regulates smooth (Berk et al 1989;Geisterfer et al 1988) and cardiac muscle growth (Sadoshima et al 1993;Ishigai et al 1997). ACE inhibitors have been shown to inhibit hypertrophy in overloaded muscle, which also suggests a role for angiotensin II in skeletal muscle hypertrophy (Gordon et al 2001;Westerkamp and Gordon 2005).…”