Effects of ovariectomy and hormone replacement on submucosal collagen and blood vessels of the anal canal of rats

Mensah-Brown, Eric; Rizk, Diaa E. E.; Patel, Mahendra; Chandranath, S.I.; Adem, Abdu

doi:10.1111/j.1463-1318.2004.00715.x

Cited by 9 publications

(14 citation statements)

References 27 publications

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“…Changes in types I to III collagen ratio correlate with changes in the mechanical properties because type I is more rigid while type III contributes more to elastic properties [13]. Hence, decreased collagen I/III ratio is associated with reduced urethral and anal canal closure function [7,[13][14][15]. Both estrogen deficiency and ageing independently and negatively influences the submucosal urethral and anal canal blood vessel counts and collagen I/III ratio in anatomical, experimental and clinical studies, similar to our findings [4,11,12,14,15].…”

Section: Discussionsupporting

confidence: 77%

“…Hence, decreased collagen I/III ratio is associated with reduced urethral and anal canal closure function [7,[13][14][15]. Both estrogen deficiency and ageing independently and negatively influences the submucosal urethral and anal canal blood vessel counts and collagen I/III ratio in anatomical, experimental and clinical studies, similar to our findings [4,11,12,14,15]. In fact, ghrelin and its receptor are expressed in human microvascular endothelial cells and rat osteoblasts where ghrelin stimulates endothelial cell proliferation, migration, and angiogenesis as well as osteoblastic synthesis of collagen type I, as seen in this study [19,20].…”

Section: Discussionmentioning

confidence: 99%

“…We did not, however, compare the effect of both hormones on postovariectomy vessel number in old as opposed to young adult rats. We did not also investigate whether these hormones can influence a second continence mechanism, the relative concentration of submucosal urethral and anal canal collagen fibers types I and III or the collagen I/III ratio [7,[13][14][15]. Although the presence of estrogen receptors was previously demonstrated by our group in the submucosa of the urethra and anal canal of rats [14,15], the expression of ghrelin receptors in these structures was not previously studied.…”

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confidence: 99%

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Combined estrogen and ghrelin administration restores number of blood vessels and collagen type I/III ratio in the urethral and anal canal submucosa of old ovariectomized rats

et al. 2007

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We compare the effects of estrogen and/or ghrelin on vascular counts and collagen I/III ratio of urethral and anal canal submucosa in old vs young-adult ovariectomized rats. Ovariectomized Fisher 344 rats (18 and 3 months old, n = 24 x 2) received 42 daily intraperitoneal 17-ss estradiol (10 microg/kg), ghrelin (2 microg/kg), both, or vehicle (n = 6 x 4 per group). Blood vessel counts and collagen I/III ratio were measured, respectively, by light microscopy and Western blot analysis with immunohistochemistry of ghrelin receptors. Estrogen significantly increased urethral and anal vascular counts and collagen I/III ratio in young-adult rats. In old rats, only combined estrogen/ghrelin administration significantly increased both variables. This was not observed with estrogen or ghrelin separately. Ghrelin receptors were immunostained in urethral and anal submucosa of all samples. Combined estrogen/ghrelin administration restored postovariectomy urethral and anal canal submucosal vessel number and collagen I/III ratio in old rats suggesting independent ageing effect.

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Section: Discussionsupporting

confidence: 77%

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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Combined estrogen and ghrelin administration restores number of blood vessels and collagen type I/III ratio in the urethral and anal canal submucosa of old ovariectomized rats

et al. 2007

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“…The increase of collagen type III in response to estrogen administration was found in hearts of aged and Dahl salt-sensitive rats (8,61). Similar estrogenic effects on collagen III were demonstrated in the arteries and other tissues of ovariectomized animals (7,10,15,24,36,47). The mechanisms of enhanced collagen type III expression due to estrogen treatment are still unknown, but they are likely related to the changes in MMPs and TIMPs expression that we Fig.…”

Section: Discussionmentioning

confidence: 60%

Estrogen improves TIMP-MMP balance and collagen distribution in volume-overloaded hearts of ovariectomized females

Voloshenyuk

Gardner

2010

American Journal of Physiology-Regulatory, Integrative and Comp

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Our previous studies demonstrate that 17␤-estradiol limits chronic volume overload-induced hypertrophy and improves heart function in ovariectomized rats. One possible cardioprotective mechanism involves the interaction between estrogen, estrogen receptors, and proteins of the extracellular matrix (ECM). The impact of estrogen deficiency and replacement on left ventricular (LV) hypertrophy and ECM protein expression was studied using five female rat groups: intact sham-operated, ovariectomized sham-operated, intact with volume overload, ovariectomized with volume overload, and ovariectomized with volume overload treated with estrogen. After 8 wk, LV protein extracts were evaluated by Western blot analysis for matrix metalloproteinase-2 (MMP-2) and MMP-9, MT1-MMP, tissue inhibitors of MMPs (TIMP)-1, TIMP-2, TIMP-3 and TIMP-4, collagens type I and III, and estrogen receptor ␣ and ␤ expression. MMP proteolytic activity was assessed by zymography. All volume-overloaded groups exhibited LV hypertrophy, which was associated with a loss of interstitial collagen and perivascular fibrosis. After 8 wk of volume overload, 70% of ovariectomized rats developed heart failure, in contrast to only one intact rat. A downregulation of MMP-2, estrogen receptor-␣ (ER␣), and ER␤, and upregulation of MMP-9 and MT1-MMP were found in the volume-overloaded hearts of ovariectomized rats. Estrogen treatment improved TIMP-2/MMP-2 and TIMP-1/MMP-9 protein balance, restored ER␣ expression, and prevented MMP-9 activation, perivascular collagen accumulation and development of heart failure. However, estrogen did not fully restore ER␤ expression and did not prevent the increase of MMP-9 expression or loss of interstitial collagen. These results support that estrogen limits undesirable ECM remodeling and LV dilation, in part, through modulation of ECM protein expression in volume-overloaded hearts of ovariectomized rats. extracellular matrix remodeling; ovariectomy; gender; hypertrophy; hormone; collagen; MT1-MMP; ventricle THE RISKS AND BENEFITS ASSOCIATED with estrogen replacement therapy remain uncertain. Conflicting results regarding the effect of estrogen replacement on the outcome of cardiovascular disease have been obtained from population studies, animal models, and clinical trials (2,16,20,21,32,33,61). The inconsistency of these findings demonstrates the lack of understanding of the mechanisms by which estrogen exerts its beneficial effects on the cardiovascular system. Using a rodent model, we demonstrated that hearts of intact female rats are resistant to chronic volume overload-induced adverse cardiac remodeling and dysfunction (12). This apparent cardioprotection is lost following ovariectomy (6). Estrogen replacement delays the development of left ventricular (LV) hypertrophy and dilation, and it prevents the onset of congestive heart failure (CHF) in ovariectomized rats with volume overload (13). However, the mechanisms of estrogen's protective effects in prevention of adverse myocardial remodeling remain unclear.Changes in extra...

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“…However, our data demonstrated that 28 days following PTCA or stenting, the total number of VSMC did not differ significantly from 17βE-treated segments, as compared to vehicle segments in both regions (table 1), which suggests a direct role for estrogen in the collagen synthesis/degradation process. Previous experiments reported that collagen type I increased significantly after ovariectomy and was normalized with estrogen treatment [28]. Estrogens could act on collagen expression through different mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Local Delivery of 17-Beta-Estradiol Modulates Collagen Content in Coronary Porcine Arteries after PTCA and Stent Implantation

et al. 2008

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Background: Percutaneous transluminal coronary angioplasty (PTCA) and stent implantation are associated with intimal hyperplasia and extracellular matrix (ECM) accumulation, resulting in restenosis. We showed that local delivery of 17-beta-estradiol (17βE) reduced restenosis following PTCA and stent implantation by 47 and 23%, respectively. Because estrogens decreased type I and type III collagen synthesis in vitro, we hypothesized that local delivery of 17βE may influence intimal hyperplasia formation by modulating ECM expression. Methods: Porcine coronary arteries underwent PTCA or stenting and were randomly assigned to 17βE or placebo. After 28 days, animals were sacrificed for histology and collagen type I and III content analysis. Results: Both collagen subtypes increased in the media by 1.7 to 2.6-fold after PTCA and by 15.7 to 16.1-fold after stenting, as compared to PTCA segments. In the neointima, the ratio of collagen type III to type I was 2.7 in stented arteries and only 0.3 in PTCA arteries. In the neointima of 17βE-treated animals, collagen type I (but not type III) content upregulation was limited by 53% after PTCA and by 74% after stenting. Conclusion: Local delivery of 17βE reduces restenosis, in part by decreasing the density of collagen type I in the neointima in PTCA and stented arteries.

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Effects of ovariectomy and hormone replacement on submucosal collagen and blood vessels of the anal canal of rats

Abstract: Oestrogen and progesterone have synergistic effects on collagen types I and III and probably antagonistic effects on the vascular plexus of the anal canal submucosa in adult female rats.

Cited by 9 publications

References 27 publications

Combined estrogen and ghrelin administration restores number of blood vessels and collagen type I/III ratio in the urethral and anal canal submucosa of old ovariectomized rats

Combined estrogen and ghrelin administration restores number of blood vessels and collagen type I/III ratio in the urethral and anal canal submucosa of old ovariectomized rats

Estrogen improves TIMP-MMP balance and collagen distribution in volume-overloaded hearts of ovariectomized females

Local Delivery of 17-Beta-Estradiol Modulates Collagen Content in Coronary Porcine Arteries after PTCA and Stent Implantation

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