Estrogen Reduces Myointimal Proliferation After Balloon Injury of Rat Carotid Artery

Chen, Shi-Juan; Li, Huaibin; Durand, Joan; Oparil, Suzanne; Chen, Yiu-Fai

doi:10.1161/01.cir.93.3.577

Cited by 227 publications

(153 citation statements)

References 29 publications

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“…A previous study showed that this dose of E2 resulted in physiological levels of circulating E2 in rats after OVX. 24 Echocardiographic and hemodynamic studies, histological analyses, immunohistostaining and real-time RT-PCR were performed as described above.…”

Section: Studymentioning

confidence: 99%

Enhanced cardiac inflammation and fibrosis in ovariectomized hypertensive rats: a possible mechanism of diastolic dysfunction in postmenopausal women

et al. 2011

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Diastolic dysfunction is more prevalent in individuals with hypertension, particularly postmenopausal women; however, the pathogenesis of diastolic dysfunction remains unknown. Pressure overload activates cardiac inflammation, which induces myocardial fibrosis and diastolic dysfunction in rats with a suprarenal aortic constriction (AC). Therefore, we examined the effects of bilateral ovariectomy (OVX) on left ventricle (LV) remodeling, diastolic dysfunction and cardiac inflammation in hypertensive female rats. Rats were randomized to OVX+AC, OVX and AC groups as well as a Control group receiving sham operations for both the procedures. Rats underwent OVX at 6 weeks and AC at 10 weeks (Day 0). At Day 28, OVX did not appear to affect arterial pressure, cardiac hypertrophy or LV fractional shortening in AC rats. However, OVX increased myocardial fibrosis, elevated LV end-diastolic pressure and reduced the transmitral Doppler spectra early to late filling velocity ratio in AC rats. AC-induced transient myocardial monocyte chemoattractant protein-1 expression and macrophage infiltration, both of which peaked at Day 3 and were augmented and prolonged by OVX. At Day 28, dihydroethidium staining revealed superoxide generation in the intramyocardial arterioles in the OVX+AC group but not in the AC group. NOX1, a functional subunit of nicotinamide adenine dinucleotide phosphate oxidase, was upregulated only in the OVX+AC group at Day 28. Chronic 17b-estradiol replacement prevented the increases in macrophage infiltration, NOX1 upregulation, myocardial fibrosis and diastolic dysfunction in OVX+AC rats. In conclusion, we suggest that estrogen deficiency augments cardiac inflammation and oxidative stress and thereby aggravates myocardial fibrosis and diastolic dysfunction in hypertensive female rats. The findings provide insight into the mechanism underlying diastolic dysfunction in hypertensive postmenopausal women. Hypertension Research (2011) 34, 496-502; doi:10.1038/hr.2010; published online 20 January 2011Keywords: estradiol; gender medicine; macrophage; myocardial fibrosis; oxidative stress INTRODUCTIONThe ejection fraction of the left ventricle (LV) is normal in approximately half of all patients with congestive heart failure, which indicates that impaired diastolic function in these patients is the major cause of heart failure. [1][2][3] Hypertension is the most common coexisting disease in patients with diastolic heart failure. Diastolic heart failure is more prevalent in women than in men, especially in postmenopausal hypertensive women, which may be due to decreased estrogen levels. 2,3 Determinants of diastolic function include active myocardial relaxation and passive properties of the LV wall. 2 Sequestration of calcium and cross-bridge uncoupling after systole are involved in the active process of relaxation. Previous studies have shown that estrogen

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Section: Studymentioning

confidence: 99%

Enhanced cardiac inflammation and fibrosis in ovariectomized hypertensive rats: a possible mechanism of diastolic dysfunction in postmenopausal women

et al. 2011

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“…The animals receiving E 2 replacement therapy were implanted with E 2 (Sigma, 5 mg)-filled silastic tubes as described previously (28,29). This dose of E 2 yields circulating estradiol levels that are in the peak physiologic range (30).…”

Section: Ovx Estrogen Replacement and Plasma Estradiol Levelsmentioning

confidence: 99%

Glomerulosclerosis and Tubulointerstitial Fibrosis are Attenuated with 17β-Estradiol in the Aging Dahl Salt Sensitive Rat

Maric¹,

Sandberg²,

Hinojosa‐Laborde³

2004

Journal of the American Society of Nephrology

186

130

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Abstract. This study examined the effects of estrogen deficiency by ovariectomy (OVX) and 17␤-estradiol (E 2 ) replacement (OVXϩE 2 ) on glomerulosclerosis and tubulointerstitial fibrosis and the mechanisms contributing to these changes, including expression of collagen type IV and laminin, transforming growth factor-␤ (TGF-␤), and activity of matrix metalloproteinases (MMP) in the kidneys of young (4 mo [4M]) and aged (12 mo [12M]) Dahl salt-sensitive (DSS) rats maintained on a low-salt (0.1% NaCl) diet. While normal renal morphology was observed in the 4M rats in all treatment groups, moderate to severe glomerulosclerosis (glomerulosclerotic index [GSI]: 4M, 0.22 Ϯ 0.09 versus 12M, 1.43 Ϯ 0.17; P Ͻ 0.001) and cortical tubulointerstitial fibrosis (CTIFI: 4M, 0 versus 12M, 57.1 Ϯ 4.9; P Ͻ 0.01) was observed in the 12M rats. The severity of glomerulosclerosis and cortical tubulointerstitial fibrosis in the 12M group was augmented with OVX (GSI, 3.27 Ϯ 0.34; CTIFI, 74.4 Ϯ 9.2; P Ͻ 0.01 versus Intact at 12M) and attenuated with E 2 replacement ([GSI], 1.09 Ϯ 0.09; CTIFI, 49.2 Ϯ 6.8). In the 12M animals, OVX was also associated with increased deposition and expression of laminin (Intact, 228.1 Ϯ 6.7; OVX, 277.4 Ϯ 9.6 AU; P Ͻ 0.01), increased expression of TGF-␤ (Intact, 85.0 Ϯ 23.0; OVX, 178.0 Ϯ 20.5 AU; P Ͻ 0.001), and decreased activity of cortical MMP-9 (Intact, 3.8 Ϯ 0.8; OVX, 2.4 Ϯ 0.6 AUC; P Ͻ 0.01). E 2 replacement opposed these effects (laminin, 229.9 Ϯ 6.2 AU; TGF-␤, 101.3 Ϯ 25.2 AU; MMP-9, 5.2 Ϯ 0.2 AUC). The severity of the disease in the 12M rats correlated with a modest decrease in creatinine clearance (Intact, 0.26 Ϯ 0.01; OVX, 0.22 Ϯ 0.01; OVXϩE 2 , 0.28 Ϯ 0.01 mg/min per 100 g) and increase in BUN (Intact, 20.3 Ϯ 2.1; OVX, 32.6 Ϯ 5.1; OVXϩE 2 , 24.3 Ϯ 2.4 mg/dl). The authors conclude that E 2 is renoprotective in the aging DSS rat by attenuating glomerulosclerosis and tubulointerstitial fibrosis.The rate of progression of cardiovascular and renal disease and hypertension increases with age and is lower in premenopausal women compared with age-matched men (1-3). Interestingly, a re-evaluation of the Modification of Diet in Renal Disease (MDRD) study showed that the differences in the rate of decline of renal function between men and women is reduced after age 52 yr (their dividing point) (4), suggesting that menopause may affect the progression of renal disease in women; however, no studies to date have clearly demonstrated this point, suggesting that our understanding of the contribution of ovarian hormones to the development of age-related disease processes remains unclear. The Women's Health Initiative (WHI) reported that hormone replacement therapy with the estrogen-progesterone combination Prempro (conjugated equine estrogen and progestin) causes a slight increase in the risk of cardiovascular disease in a large population of postmenopausal women (5,6). However, numerous studies indicate that estrogen alone has cardiovascular protective effects. Estrogen improves serum lipid levels, increases end...

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“…Beside its beneficial impact on the lipid profile, estrogen stimulates nitric oxide production by endothelial cells (139,140). Nitric oxide has an antiproliferative effect on SMCs and it downregulates the expression of the proto-oncogene c-myc, which is involved in SMC proliferation (142). Moreover, estradiol promotes vascular healing by stimulation of the estrogen receptor alpha, which improves re-endothelization.…”

Section: Estradiolmentioning

confidence: 99%

The cell cycle: A critical therapeutic target to prevent vascular proliferative disease

Charron

Nili

Strauss

2006

Canadian Journal of Cardiology

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Estrogen Reduces Myointimal Proliferation After Balloon Injury of Rat Carotid Artery

Cited by 227 publications

References 29 publications

Enhanced cardiac inflammation and fibrosis in ovariectomized hypertensive rats: a possible mechanism of diastolic dysfunction in postmenopausal women

Enhanced cardiac inflammation and fibrosis in ovariectomized hypertensive rats: a possible mechanism of diastolic dysfunction in postmenopausal women

Glomerulosclerosis and Tubulointerstitial Fibrosis are Attenuated with 17β-Estradiol in the Aging Dahl Salt Sensitive Rat

The cell cycle: A critical therapeutic target to prevent vascular proliferative disease

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