Vascular smooth muscle cell NAD(P)H oxidase activity during the development of hypertension: Effect of angiotensin II and role of insulinlike growth factor-1 receptor transactivation

Cruzado, Montserrat; Risler, Norma; Miatello, Roberto; Yao, Guoying; Schiffrin, Ernesto L.; Touyz, Rhian M.

doi:10.1016/j.amjhyper.2004.09.001

Cited by 74 publications

(59 citation statements)

References 37 publications

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“…Our results showed that significantly higher ROS exists in late-passage SMCs compared to low ROS in early passage SMCs, indicating the presence of oxidative stress in higher passage SMCs. Interestingly, stimulation with IGF-1 did not enhance the formation of ROS in either group of VSMC, which is consistent with previous results [36,37]. Mitochondria have been proposed as major sites where oxidative stress take place [53,54].…”

Section: Discussionsupporting

confidence: 81%

“…However, IGF-1 exposure (10 ng/ml) failed to enhance ROS formation in cells from either the early or late passages. This is in contrast to previously published studies, wherein growth factors, such as insulin and platelet-derived growth factor (PDGF) have been reported to promote ROS formation [36,37].…”

Section: Migration and Proliferation Of Different Passage Vsmcscontrasting

confidence: 54%

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Impact of Insulin-like Growth Factor-I on Migration, Proliferation and Akt-ERK Signaling in Early and Late-passages of Vascular Smooth Muscle Cells

et al. 2007

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Migration and proliferation of vascular smooth muscle cells (VSMCs) are important events in the progression of atherosclerosis. Insulin-like growth factor I (IGF-1) possesses both antiapoptotic and mitogenic/motogenic effects in VSMCs although the influence of life cycle on IGF-1-induced effects is unclear. This study was designed to evaluate the effect of IGF-1 on migration, proliferation, and signaling mechanisms in VSMCs from early (3-5) to late (20-22) passages. Migration, proliferation, and cell survival were measured using monolayer wounding, 3 [H]-thymidine incorporation and MTT assay, respectively. Akt and ERK, which are critical to proliferation, differentiation and migration, were examined using Western blot analysis. DCF-DA fluorescence was used to quantify Reactive Oxygen Species (ROS) production. Latepassage VSMCs exhibited significantly higher basal cell proliferation and enhanced sensitivity to IGF-1-stimulated migration compared to cells from early-passages. Phosphorylated Akt and ERK levels were significantly higher in late-passage cells compared to early-passage, which was further enhanced by IGF-1 treatment. Late-passage cells exhibited higher levels of ROS production compared to early-passage, cells. IGF-1 did not significantly alter ROS levels in either passage. Expression of the cell cycle regulator p53, p21, and p16 was not affected by repeated passaging of cells. These results indicated that repeated passaging of VSMCs exhibits a phenotype which has higher proliferative capacity. Activation of trophic signaling molecules such as ERK1/2 and Akt and generation of ROS may represent the mechanisms by which repeated passages of VSMCs acquire a motogenic and mitogenic phenotype.

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Section: Discussionsupporting

confidence: 81%

Section: Migration and Proliferation Of Different Passage Vsmcscontrasting

confidence: 54%

Impact of Insulin-like Growth Factor-I on Migration, Proliferation and Akt-ERK Signaling in Early and Late-passages of Vascular Smooth Muscle Cells

et al. 2007

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“…21 This is consistent with the finding that the activity of the glutathione peroxidase, which protects from oxidative damages, is significantly reduced in kidneys of SHR from the age of 8 week onwards. 22 Besides, obvious cardiac hypertrophy is developed around week 8, for example, together with an activation of the cardiac endothelin system.…”

Section: Discussionsupporting

confidence: 81%

Hypertension augments cardiac Toll-like receptor 4 expression and activity

et al. 2011

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Hypertension causes cardiac hypertrophy characterized by low-grade inflammation. Toll-like receptors (TLRs), members of the innate immune system, contribute to cardiac failure. We hypothesized that hypertension is accompanied by enhanced TLR4 expression and activity. Cardiac TLR4 expression was determined in untreated spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY;4,8, 16 weeks). Besides, hearts of 8-week-old rats were stimulated with the endogenous TLR4 ligand heparansulfate (HS); the proinflammatory mRNA pattern was assessed (tumor necrosis factor-a (TNF-a), interleukin (IL)-6, monocyte chemotactic protein (MCP)-1). Additionally, we induced hypertension in WKY by L-NAME (N x -nitro-L-argininemethylester hydrochloride). In both hypertension models the effect of ramipril on TLR4 density was assessed. Cardiac TLR4 distribution was investigated by fluorescence-activated cell sorting analysis. Blood pressure (BP) and heart weight/body weight ratio (HW/BW) were elevated in SHR. Constitutive TLR4 expression was augmented in adolescent and adult, but not young SHR compared with WKY. TLR4 staining was pronounced in cardiomyocytes. HS entailed an aggravated TNF-a and IL-6 mRNA response in cardiac tissue, which was significantly pronounced in SHR. Ramipril (10 mg kg À1 per day) reduced BP, HW/BW and TLR4 expression in SHR. L-NAME also augmented TLR4 expression in WKY. Ramipril (1 mg kg À1 per day) lowered BP but TLR4 expression remained unaffected. High-dose ramipril (10 mg kg À1 per day) however decreased TLR4 expression. Starting from adolescence SHR demonstrated enhanced cardiac TLR4 expression. TLR4 was also upregulated in L-NAME induced hypertension. Thus, enhanced TLR4 expression might be linked to the development and maintenance of hypertension. Finally, the antihypertensive, anti-inflammatory action of angiotensin-converting-enzyme inhibition had no effect on TLR4 expression in therapeutic doses but in a high-dose model.

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“…Thus, to determine whether K ϩ channel current normalization by GSH o was mediated by a phosphorylation mechanism, the GSH o protocol was repeated after pretreating myocytes from post-MI hearts for 30 min with one of two pan-specific inhibitors of tyrosine kinase: genistein (1 mol/l) or lavendustin A (10 mol/l). We also examined the effect of AG1024 (100 nmol/l), a specific inhibitor of insulin receptor tyrosine kinase (9). As shown in Fig.…”

Section: Signaling Mechanisms Involved In Kmentioning

confidence: 99%

Role of γ-glutamyl transpeptidase in redox regulation of K⁺ channel remodeling in postmyocardial infarction rat hearts

Zheng¹,

Tang²,

Zimmerman³

et al. 2009

American Journal of Physiology-Cell Physiology

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-␥-Glutamyl transpeptidase (␥-GT) is a key enzyme in GSH metabolism that regulates intracellular GSH levels in response to extracellular GSH (GSHo). The objective of this study was to identify the role of ␥-GT in reversing pathogenic K ϩ channel remodeling in the diseased heart. Chronic ventricular dysfunction was induced in rats by myocardial infarction (MI), and studies were done after 6 -8 wk. Biochemical assays of tissue extracts from post-MI hearts revealed significant increases in ␥-GT activity in left ventricle (47%) and septum (28%) compared with sham hearts, which paralleled increases in protein abundance and mRNA. Voltage-clamp studies of isolated left ventricular myocytes from post-MI hearts showed that downregulation of transient outward K ϩ current (Ito) was reversed after 4 -5 h by 10 mmol/l GSHo or N-acetylcysteine (NACo), and that the effect of GSHo but not NACo was blocked by the ␥-GT inhibitors, acivicin or S-hexyl-GSH. Inhibition of ␥-glutamylcysteine synthetase by buthionine sulfoximine did not prevent upregulation of Ito by GSHo, suggesting that intracellular synthesis of GSH was not directly involved. However, pretreatment of post-MI myocytes with an SOD mimetic [manganese (III) tetrapyridylporphyrin] and catalase completely blocked recovery of Ito by GSHo. Confocal microscopy using the fluorogenic dye 2Ј,7Ј-dichlorodihydrofluorescein diacetate confirmed that GSHo increased reactive oxygen species (ROS) generation by post-MI myocytes and to a lesser extent in myocytes from sham hearts. Furthermore, GSHomediated upregulation of Ito was blocked by inhibitors of tyrosine kinase (genistein, lavendustin A, and AG1024) and thioredoxin reductase (auranofin and 13-cis-retinoic acid). These data suggest that GSHo elicits ␥-GT-and ROS-dependent transactivation of tyrosine kinase signaling that upregulates K ϩ channel activity or expression via redox-mediated mechanisms. The signaling events stimulated by ␥-GT catalysis of GSHo may be a therapeutic target to reverse pathogenic electrical remodeling of the failing heart. glutathione; voltage-dependent K ϩ channel; thioredoxin; transient outward current CHRONIC MYOCARDIAL INFARCTION (MI)-induced ventricular dysfunction elicits a pathogenic process of electrical remodeling that is characterized at the myocyte level by downregulation of K ϩ channel expression. This change in electrophysiological phenotype is proposed to contribute to arrhythmogenic abnormalities in repolarization (5) and cellular alterations in Ca 2ϩ handling that impact contractile function (45). Recent studies from our laboratory suggest that redox-mediated mechanisms underlie K ϩ channel remodeling by oxidative stress in the rat heart with chronic MI (36, 37). It is proposed that redox control of K ϩ channels in heart involves endogenous thiol oxidoreductase systems, particularly 1) the thioredoxin (Trx) system, which operates with thioredoxin reductase (TrxR) and NADPH to catalyze the reduction of protein disulfides (20,30,32,40,47), and 2) the glutaredoxin (Grx) system, which uses re...

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Vascular smooth muscle cell NAD(P)H oxidase activity during the development of hypertension: Effect of angiotensin II and role of insulinlike growth factor-1 receptor transactivation

Abstract: Basal and Ang II-induced NAD(P)H-driven ROS generation are enhanced in VSMCs from SHR during development of hypertension, but not in cells from prehypertensive rats. Transactivation of IGF-1R by Ang II may be important in vascular oxidative excess in the development of hypertension in SHR.

Cited by 74 publications

References 37 publications

Impact of Insulin-like Growth Factor-I on Migration, Proliferation and Akt-ERK Signaling in Early and Late-passages of Vascular Smooth Muscle Cells

Impact of Insulin-like Growth Factor-I on Migration, Proliferation and Akt-ERK Signaling in Early and Late-passages of Vascular Smooth Muscle Cells

Hypertension augments cardiac Toll-like receptor 4 expression and activity

Role of γ-glutamyl transpeptidase in redox regulation of K⁺ channel remodeling in postmyocardial infarction rat hearts

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Vascular smooth muscle cell NAD(P)H oxidase activity during the development of hypertension: Effect of angiotensin II and role of insulinlike growth factor-1 receptor transactivation

Cited by 74 publications

References 37 publications

Impact of Insulin-like Growth Factor-I on Migration, Proliferation and Akt-ERK Signaling in Early and Late-passages of Vascular Smooth Muscle Cells

Impact of Insulin-like Growth Factor-I on Migration, Proliferation and Akt-ERK Signaling in Early and Late-passages of Vascular Smooth Muscle Cells

Hypertension augments cardiac Toll-like receptor 4 expression and activity

Role of γ-glutamyl transpeptidase in redox regulation of K+ channel remodeling in postmyocardial infarction rat hearts

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Role of γ-glutamyl transpeptidase in redox regulation of K⁺ channel remodeling in postmyocardial infarction rat hearts