20-Hydroxyeicosatetraenoic Acid Mediates Angiotensin II–Induced Phospholipase D Activation in Vascular Smooth Muscle Cells

Parmentier, Jean-Hugues; Muthalif, Mubarack M.; Nishimoto, Andrew T.; Malik, Kafait U.

doi:10.1161/01.hyp.37.2.623

Cited by 37 publications

(42 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In cultured vascular smooth muscle cells from adult rabbits (19) and rats (33) as well as in isolated renal arterioles (31), 20-HETE induces the phosphorylation of ERK1/2, a MAPK that plays a pivotal role in the proliferation induced by the activation of receptor tyrosine kinases and G proteincoupled receptors (9). Blockade of the formation of 20-HETE attenuated norepinephrine-induced and ANG II-induced ERK1/2 phosphorylation, suggesting that 20-HETE may serve as a second messenger of these growth factors (20,24). The same investigators also showed that 20-HETE contributed to ANG II-induced neointimal thickening in the injured carotid artery (43).…”

Section: Discussionmentioning

confidence: 99%

20-HETE induces remodeling of renal resistance arteries independent of blood pressure elevation in hypertension

Ding

García

et al. 2013

American Journal of Physiology-Renal Physiology

View full text Add to dashboard Cite

-Hydroxyeicosatetraenoic acid (20-HETE) is a cytochrome P-450 (Cyp)-derived arachidonic acid metabolite that has been shown to increase smooth muscle contractions and proliferation, stimulate endothelial dysfunction and activation, and promote hypertension. We examined if 20-HETE contributes to microvascular remodeling in hypertension. In Sprague-Dawley rats, administration of the 20-HETE biosynthesis inhibitor HET0016 or the ,15(Z)-dienoic acid (20-HEDE) prevented 5␣-dihydrotestosterone (DHT)-induced increases in blood pressure as well as abrogated DHT-induced increases in the media-to-lumen ratio (M/L), media thickness, and collagen IV deposition in renal interlobar arteries. Reserpine prevented blood pressure elevation in DHT-treated rats but did not affect microvascular remodeling (M/L, media thickness, and collagen deposition); under these conditions, treatment with the 20-HETE antagonist attenuated microvascular remodeling, suggesting that 20-HETE contributes to DHT-induced vascular remodeling independent of blood pressure elevation. In Cyp4a14 Ϫ/Ϫ mice, which display androgen-driven and 20-HETE-dependent hypertension, treatment with the 20-HETE antagonist abolished remodeling of renal resistance arteries measured as media thickness (24 Ϯ 1 vs. 15 Ϯ 1 m) and M/L (0.29 Ϯ 0.03 vs. 0.17 Ϯ 0.01). Moreover, in Cyp4a12 transgenic mice in which the expression of Cyp4a12-20-HETE synthase is driven by a tetracycline-sensitive promoter, treatment with doxycycline resulted in blood pressure elevation (140 Ϯ 4 vs. 92 Ϯ 5 mmHg) and a significant increase in remodeling of renal resistance arteries (media thickness: 23 Ϯ 1 vs. 16 Ϯ 1 m; M/L: 0.39 Ϯ 0.04 vs. 0.23 Ϯ 0.02); these increases were abrogated by cotreatment with 20-HEDE. This study demonstrated that 20-HETE is a key regulator of microvascular remodeling in hypertension; its effect is independent of blood pressure elevation and androgen levels. 20-hydroxyeicosatetraenoic acid; cytochrome P-450 4A; blood pressure; androgen VASCULAR REMODELING of large and small arteries contributes to the development and complications of hypertension (25). This process renders arteries stiffer and thicker, leading to detrimental effects on blood pressure regulation (14). Structural alterations of the microcirculation, of which the media-to-lumen ratio (M/L) is the most important predictor, are likely to occur in renal microvessels, as previously shown in experimental models of hypertension (7), including spontaneously hypertensive rats (SHRs), DOCA-salt rats, and one-kidney, one-clip Goldblatt hypertensive rats (12). The mechanisms that contribute to arterial remodeling in hypertension are numerous and include stimulation of growth and apoptosis and increased inflammation and fibrosis. Numerous autacoids have been implicated as mediators of arterial remodeling in hypertension. The most prominent is ANG II, which has been shown to exert the capacity of stimulating vasoconstriction, smooth muscle growth, production of inflammatory cytokines and chemokines, and activating extracellul...

show abstract

Section: Discussionmentioning

confidence: 99%

20-HETE induces remodeling of renal resistance arteries independent of blood pressure elevation in hypertension

Ding

García

et al. 2013

American Journal of Physiology-Renal Physiology

View full text Add to dashboard Cite

show abstract

“…Several proteins have been involved in mediating PLD activation elicited by ANG II in VSMC such as heterotrimeric and small G proteins (1, 38) and phospholipase A 2 (27). PLD may contribute to the functional effects of ANG II on VSMC through the formation of phosphatidic acid and/or its metabolites (27)(28)(29)(30). ANG II selectively activates PLD2 isoform in VSMC (27).…”

mentioning

confidence: 99%

“…PLD may contribute to the functional effects of ANG II on VSMC through the formation of phosphatidic acid and/or its metabolites (30). Several proteins have been involved in mediating PLD activation elicited by ANG II in VSMC such as heterotrimeric and small G proteins (1,38) and phospholipase A 2 (27). PLD may contribute to the functional effects of ANG II on VSMC through the formation of phosphatidic acid and/or its metabolites (27)(28)(29)(30).…”

mentioning

confidence: 99%

“…PLD may contribute to the functional effects of ANG II on VSMC through the formation of phosphatidic acid and/or its metabolites (27)(28)(29)(30). ANG II selectively activates PLD2 isoform in VSMC (27). However, the exact signaling pathway regulating ANG II-induced PLD2 activation and its functional significance in VSMC has not yet been established.…”

mentioning

confidence: 99%

“…Culture of VSMC. Male Sprague-Dawley rats (Charles River Laboratories, Wilmington, MA), maintained according to our Institutional Guidelines and by the Animal Care Committee at the University of Tennessee Health Science Center, were anesthetized with pentobarbital sodium (Sigma); the aorta was removed, and VSMC were isolated and cultured as previously described (27).VSMC between passages 3 and 8 were used for experiments.…”

mentioning

confidence: 99%

See 2 more Smart Citations

ANG II stimulates phospholipase D through PKCζ activation in VSMC: implications in adhesion, spreading, and hypertrophy

Parmentier

Pavicevic

Malik

2006

American Journal of Physiology-Heart and Circulatory Physiology

Self Cite

View full text Add to dashboard Cite

lates phospholipase D (PLD) activity and growth of vascular smooth muscle cells (VSMC). The atypical protein kinase C-(PKC) plays a central role in the regulation of cell survival and proliferation. This study was conducted to determine the relationship between ANG II-induced activation of PKC and PLD and their implication in VSMC adhesion, spreading, and hypertrophy. ANG II stimulated PKC activity with maximal activation at 30 s followed by a decline in its activity to 45% above basal at 5 min. Inhibition of PKC activity with a myristoylated pseudosubstrate peptide or overexpression of a kinase-inactive form of PKC decreased ANG II-induced PLD activity. Moreover, depletion of PKC with selective antisense oligonucleotides also decreased ANG II-induced PLD activity. Interaction between PLD2 and PKC in VSMC was detected by coimmunoprecipitation. ANG II-induced PLD activity was inhibited by the primary alcohol n-butanol but not the tertiary alcohol t-butanol. The functional significance of PKC and PLD2 in VSMC adhesion, spreading, and hypertrophy was investigated. Inhibition of PKC and PLD2 activity or expression attenuated VSMC adhesion to collagen I and ANG II-induced cell spreading and hypertrophy. These results demonstrate that ANG II-induced PLD activation is regulated by PKC and suggest a crucial role of PKC-dependent PLD2 in VSMC functions such as adhesion, spreading, and hypertrophy, which are associated with the pathogenesis of atherosclerosis and malignant hypertension. vascular smooth muscle cells; protein kinase C; angiotensin II PHOSPHOLIPASE D (PLD) catalyzes the hydrolysis of phosphatidylcholine into phosphatidic acid and choline. Activation of PLD by neurotransmitters, hormones, or growth factors has been implicated in a wide range of biological actions, including cellular trafficking, inflammatory and immune response, mitogenesis, cellular differentiation, and apoptosis (23). To date, two PLD isoforms, PLD1 and PLD2, have been cloned and characterized (7, 11). PLD1 is activated by direct binding of classical PKCs and small G proteins of Arf and Rho family (13,26). PLD2 requires phosphatidylinositol 4,5-bisphosphate and is not or is less responsive to Arf, Rho, and protein kinase C (PKC) than PLD1 (4, 19).ANG II contributes to the regulation of vascular tone and blood pressure (5). Hypertrophy of vascular smooth muscle cells (VSMC) induced by ANG II is an important feature of hypertension, and the structural changes in the vessel wall contribute to the increase in vascular resistance (25). VSMC response to ANG II, i.e., hyperplasia vs. hypertrophy, is determined by autocrine expression of transforming growth factor-␤ (TGF-␤) (12). ANG II in most cases does not increase DNA synthesis in VSMC. However, it increases protein synthesis and causes hypertrophy of confluent quiescent VSMC (3). A key event in neointima formation and atherogenesis is the migration of VSMC and fibroblasts into the intima. This is controlled by cytokines and extracellular matrix components within the microenvironment of the dis...

show abstract

Mechanisms of Arsenic Exposure-Induced Hypertension and Atherosclerosis: an Updated Overview

Balarastaghi

Rezaee

Hayes

et al. 2022

Biol Trace Elem Res

View full text Add to dashboard Cite

20-Hydroxyeicosatetraenoic Acid Mediates Angiotensin II–Induced Phospholipase D Activation in Vascular Smooth Muscle Cells

Cited by 37 publications

References 34 publications

20-HETE induces remodeling of renal resistance arteries independent of blood pressure elevation in hypertension

20-HETE induces remodeling of renal resistance arteries independent of blood pressure elevation in hypertension

ANG II stimulates phospholipase D through PKCζ activation in VSMC: implications in adhesion, spreading, and hypertrophy

Mechanisms of Arsenic Exposure-Induced Hypertension and Atherosclerosis: an Updated Overview

Contact Info

Product

Resources

About