Angiotensin II receptor antagonists prevent neointimal proliferation in a porcine coronary artery organ culture model

Wilson, David P.; Saward, Laura; Zahradka, Peter; Cheung, Po Kee

doi:10.1016/s0008-6363(98)00340-x

Cited by 48 publications

(35 citation statements)

References 59 publications

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“…These data were further supported by an ANG II-dependent increase in the nuclear localization of PCNA, which was blocked with either an AT 1 or AT 2 receptor subtype antagonist (Fig. 4), in agreement with our previous examination of bromodeoxyuridine incorporation (26).…”

Section: Resultssupporting

confidence: 92%

“…This study confirms our previous observation that neointimal formation in porcine coronary artery rings could be inhibited by PD-123319 as well as losartan following balloon-catheter injury in vitro (26). Furthermore, we have previously shown that ANG II-induced neointimal formation involves two events, cell proliferation and cell migration (14,28,29).…”

Section: Discussionsupporting

confidence: 91%

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Both AT₁and AT₂receptors mediate proliferation and migration of porcine vascular smooth muscle cells

Louis

Saward

Zahradka

2011

American Journal of Physiology-Heart and Circulatory Physiology

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Louis S, Saward L, Zahradka P. Both AT1 and AT2 receptors mediate proliferation and migration of porcine vascular smooth muscle cells. Am J Physiol Heart Circ Physiol 301: H746 -H756, 2011. First published May 27, 2011 doi:10.1152/ajpheart.00431.2010.-Angiotensin receptor antagonists have shown clinical promise in modulating vascular disease, in part by limiting smooth muscle cell proliferation and migration. The majority of studies examining the contribution of these receptors have been undertaken in cells derived from rat aorta, which primarily express the ANG II type 1 (AT1) receptor. This investigation studied the relative contribution of AT1 and ANG II type 2 (AT2) receptors to the mitogenic program of porcine smooth muscle cells. Smooth muscle cells were derived from porcine coronary artery explants. The presence of both AT1 and AT2 receptors was demonstrated through ligand binding and RT-PCR analysis. Biochemical and cellular markers of proliferation were monitored in the presence of selective receptor antagonists. Smooth muscle cell migration was measured using both wound healing and Boyden chamber migration assays. Visualization of the AT1 and AT2 receptors in growing and quiescent porcine smooth muscle cells with epifluorescence microscopy demonstrated that their subcellular distribution varied with growth state. An examination with several growth assays revealed that both AT1-specific losartan and AT2-specific PD-123319 receptor antagonists inhibited ANG II-stimulated RNA and DNA synthesis, PCNA expression, and hyperplasia. ANG II induced both directional and nondirectional cell migration. AT1 receptor antagonist treatment significantly decreased ANG II-induced directional migration only, whereas AT2 receptor antagonist treatment significantly reduced both modes of migration. Interestingly, the focal adhesion kinase inhibitor PF-573228 also blocked migration but not proliferation. Furthermore, focal adhesion kinase activation in response to ANG II was prevented only by PD-123319, indicating that this activation is downstream of the AT2 receptor. The observed role of the AT2 receptor in ANG II-induced migration was confirmed with smooth muscle cells depleted of the AT2 receptor with short hairpin RNA treatment.focal adhesion kinase; angiotensin II types 1 and 2 receptors; losartan; PD-123319; PF-573228 EXCESSIVE SMOOTH MUSCLE CELL (SMC) growth has been implicated in the development and progression of cardiovascular diseases such as atherosclerosis and hypertension. A critical mediator of these disease processes is angiotensin II (ANG II), a biologically active peptide with a broad range of physiological effects on the cardiovascular system (8). The actions of ANG II are mediated by at least two different ANG II receptors, ANG II types 1 (AT 1 ) and 2 (AT 2 ) receptors; however, the AT 1 receptor is typically regarded as the primary mediator of the vascular response to ANG II. As a consequence, many studies of SMCs have not included an analysis of the AT 2 receptor and fewer details of its biological f...

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Section: Resultssupporting

confidence: 92%

Section: Discussionsupporting

confidence: 91%

Both AT₁and AT₂receptors mediate proliferation and migration of porcine vascular smooth muscle cells

Louis

Saward

Zahradka

2011

American Journal of Physiology-Heart and Circulatory Physiology

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“…This result suggested a basal activation of AT1 receptors through intracellular angiotensin II production (Kumar et al 2007). This finding was not surprising, as a number of researchers have demonstrated that the local production of angiotensin II by smooth muscle cells is sufficient to mediate restenosis (Wilson et al 1999). In summary, these data confirm that angiotensin II plays a central role in the pathophysiology of cardiovascular diseases via the AT1 receptor by modulating the rate of growth.…”

Section: Discussionsupporting

confidence: 63%

The effect of losartan on angiotensin II-induced cell proliferation in a rat aorta smooth muscle cell line

Tambelline

Oliveira

Olchanheski

et al. 2012

Braz. arch. biol. technol.

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The success of revascularization procedures is limited by recurrent stenosis, which is a narrowing of a blood vessels that results from neo-intimal hyperplasia. The renin-angiotensin-aldosterone system has been implicated in the pathogenesis of neo-intimal hyperplasia, and a role for angiotensin II in vascular smooth muscle cell proliferation has been proposed. There are at least two high-affinity subtypes of angiotensin II receptors, AT1 and AT2, both of which are seven-transmembrane G protein-coupled receptors. We investigated the effect of losartan, an AT1receptor antagonist, on vascular smooth muscle cell proliferation using the A7r5 smooth cell line derived from rat aorta. Losartan was shown to prevent angiotensin II-induced cell proliferation, thereby suggesting that the effect of angiotensin II was mediated via AT1 receptors. These data strengthen the concept that inhibitors of the reninangiotensin system can effectively prevent recurrent stenosis.

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“…This assumption has been confirmed by organ culture studies using porcine coronary artery. Incubation of porcine coronary artery segments with FBS in vitro results in the development of a neointima associated with a compact extracellular matrix and few disruptions in the internal elastic lamina (10). In this organ culture model of coronary restenosis, because the inhibition of angiotensin II receptors effectively inhibits cell proliferation and restenosis post-angioplasty in vitro, it is suggested that angiotensin II contributes to neointimal proliferation and validates the concept that receptor antagonists could contribute to the therapeutic management of restenosis.…”

Section: -3 Other Proliferative Agentssupporting

confidence: 57%

Organ Culture as a Useful Method for Studying the Biology of Blood Vessels and Other Smooth Muscle Tissues

Ozaki

Karaki

2002

Japanese Journal of Pharmacology

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ABSTRACT-The benefit of organ culture is to retain the original structural relationship between various cell species and their interactions and enable us to study the long-term effects of exogenous stimuli. Organ culture methods have been used especially in the studies of the proliferative vascular diseases, such as atherosclerosis and restenosis. We describe here that organ culture is a useful in vitro method to study the biology of vascular and other smooth muscle organs.

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Angiotensin II receptor antagonists prevent neointimal proliferation in a porcine coronary artery organ culture model

Cited by 48 publications

References 59 publications

Both AT₁and AT₂receptors mediate proliferation and migration of porcine vascular smooth muscle cells

Both AT₁and AT₂receptors mediate proliferation and migration of porcine vascular smooth muscle cells

The effect of losartan on angiotensin II-induced cell proliferation in a rat aorta smooth muscle cell line

Organ Culture as a Useful Method for Studying the Biology of Blood Vessels and Other Smooth Muscle Tissues

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Angiotensin II receptor antagonists prevent neointimal proliferation in a porcine coronary artery organ culture model

Cited by 48 publications

References 59 publications

Both AT1and AT2receptors mediate proliferation and migration of porcine vascular smooth muscle cells

Both AT1and AT2receptors mediate proliferation and migration of porcine vascular smooth muscle cells

The effect of losartan on angiotensin II-induced cell proliferation in a rat aorta smooth muscle cell line

Organ Culture as a Useful Method for Studying the Biology of Blood Vessels and Other Smooth Muscle Tissues

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Both AT₁and AT₂receptors mediate proliferation and migration of porcine vascular smooth muscle cells

Both AT₁and AT₂receptors mediate proliferation and migration of porcine vascular smooth muscle cells