Ovariectomy increases the incidence and diameter of abdominal aortic aneurysm in a hypoperfusion-induced abdominal aortic aneurysm animal model

Miyamoto, Chie; Kugo, Hirona; Hashimoto, Keisuke; Moriyama, Tatsuya; Zaima, Nobuhiro

doi:10.1038/s41598-019-54829-0

Cited by 9 publications

(9 citation statements)

References 34 publications

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“…Destruction of the fiber component of the aortic wall was also observed in the thoracic and abdominal aortas, suggesting a possible relationship between OVX-induced dysfunction of PVAT and destruction of vascular fibers. Decrease in 17β-estradiol levels was observed in serum of OVX female rats 3) . Decreased estrogen leads to various symptoms such as metabolic syndrome and hypertension, which cause PVAT dysfunction, and leads to vascular fiber destruction, vascular dysfunction, and attenuation of the anti-contractile effect of blood vessels 20−22) .…”

Section: Discussionmentioning

confidence: 84%

“…Pathological analysis of the aortic wall of the thoracic aorta showed that OVX degraded elastic fibers and collagen fibers. Miyamoto et al reported that OVX induced degradation of vascular fibers in the abdominal aorta 3) . Johnston reported that OVX resulted in de- creased levels of smooth muscle cells (SMCs) and elastin fibers in the mouse aortic wall 10) .…”

Section: Discussionmentioning

confidence: 99%

“…In human aortas with atherosclerosis, inflammatory cells are reported to densely accumulate in PVAT adjacent to the vessel adventitia, and PVAT is suggested to have the potential to promote vascular inflammation 16,17) . OVX reportedly promotes the incidence and progression of abdominal aortic aneurysms 3) . The OVX-induced increase in abdominal aortic aneurysm incidence may be partly associated with OVX-induced dysfunction of abdominal PVAT.…”

Section: Discussionmentioning

confidence: 99%

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Ovariectomy Causes Degeneration of Perivascular Adipose Tissue

et al. 2021

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IntroductionCardiovascular disease (CVD) is a major cause of death worldwide. Sex reportedly affects the incidence and development rate of CVD. Until the age of early 40s, the incidence of CVD in women (1.3/1000 person-years) is lower than that in men (5.7/1000 person-years) of the same age 1) . However, when the age of late 60s is reached, this difference almost disappears, with an incidence of 22.1/1000 person-years for women and 26.7/1000 person-years for men 1) . The reason for the difference in pathology depending on sex is that estrogen, a female sex hormone, has a regulating effect on blood vessels 2, 3) , maintaining the integrity of blood vessels in premenopausal women. Menopause signals a decline in ovarian function, leading to a rapid decrease in estrogen, increasing the prevalence of vascular disease, and further increasing the risk of vascular disease in women with premature menopause 4,5) . Menopause is one of the risk factors for vascular disease, and understanding the vascular pathology characteristics of women is extremely important.

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Section: Discussionmentioning

confidence: 84%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Ovariectomy Causes Degeneration of Perivascular Adipose Tissue

et al. 2021

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“…In support of this theory, an observational study found that women with earlier menopause were characterized by larger AAA diameters (46). The oestrogen effect has also been demonstrated in various animal AAA models (47)(48)(49)(50). Two experimental AAA studies that compared ovariectomized mice with a sham operation group showed specifically an increased expression of MMP-9 in AAA tissue in the ovariectomized group (47,48).…”

Section: Sex Steroid Hormones: Oestrogen and Testosteronementioning

confidence: 86%

A Novel Hypothesis: A Role for Follicle Stimulating Hormone in Abdominal Aortic Aneurysm Development in Postmenopausal Women

et al. 2021

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An abdominal aortic aneurysm (AAA) is a dilatation of the abdominal aorta, which can potentially be fatal due to exsanguination following rupture. Although AAA is less prevalent in women, women with AAA have a more severe AAA progression compared to men as reflected by enhanced aneurysm growth rates and a higher rupture risk. Women are diagnosed with AAA at an older age than men, and in line with increased osteoporosis and cardiovascular events, the delayed AAA onset has been attributed to the reduction of the protective effect of oestrogens during the menopausal transition. However, new insights have shown that a high follicle stimulating hormone (FSH) level during menopause may also play a key role in those diseases. In this report we hypothesize that FSH may aggravate AAA development and progression in postmenopausal women via a direct and/or indirect role, promoting aorta pathology. Since FSH receptors (FSHR) are reported on many other cell types than granulosa cells in the ovaries, it is feasible that FSH stimulation of FSHR-bearing cells such as aortic endothelial cells or inflammatory cells, could promote AAA formation directly. Indirectly, AAA progression may be influenced by an FSH-mediated increase in osteoporosis, which is associated with aortic calcification. Also, an FSH-mediated decrease in cholesterol uptake by the liver and an increase in cholesterol biosynthesis will increase the cholesterol level in the circulation, and subsequently promote aortic atherosclerosis and inflammation. Lastly, FSH-induced adipogenesis may lead to obesity-mediated dysfunction of the microvasculature of the aorta and/or modulation of the periaortic adipose tissue. Thus the long term increased plasma FSH levels during the menopausal transition may contribute to enhanced AAA disease in menopausal women and could be a potential novel target for treatment to lower AAA-related events in women.

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“…Hypoperfusion in the aortic wall was induced as described in previous studies [ 9 , 21 , 28 ]. The infrarenal aorta was exfoliated from the perivascular adipose tissue ( Figure S1A ), and vessels branching were ligated with 5–0 silk sutures (Akiyama Seisakusyo Co., Tokyo, Japan) to block the blood supply ( Figure S1B ).…”

Section: Methodsmentioning

confidence: 99%

Time-Dependent Pathological Changes in Hypoperfusion-Induced Abdominal Aortic Aneurysm

Kugo

Sukketsiri

Tanaka

et al. 2021

Biology

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Hypoperfusion due to vasa vasorum stenosis can cause wall hypoxia and abdominal aortic aneurysm (AAA) development. Even though hypoperfusion is an important contributor toward pathological changes in AAA, the correlation between hypoperfusion and AAA is not fully understood. In this study, a time-dependent semi-quantitative pathological analysis of hypoperfusion-induced aortic wall changes was performed to understand the mechanisms underlying the gradual degradation of the aortic wall leading to AAA formation. AAA-related factors evaluated in this study were grouped according to the timing of dynamic change, and five groups were formed as follows: first group: angiotensin II type 1 receptor, endothelin-1 (ET-1), and malondialdehyde (MDA); second group: matrix metalloproteinase (MMP)-2, -9, -12, M1 macrophages (Mac387+ cells), and monocyte chemotactic protein-1; third group: synthetic smooth muscle cells (SMCs); fourth group: neutrophil elastase, contractile SMCs, and angiotensinogen; and the fifth group: M2 macrophages (CD163+ cells). Hypoxia-inducible factor-1α, ET-1, MDA, and MMP-9 were colocalized with alpha-smooth muscle actin cells in 3 h, suggesting that hypoperfusion-induced hypoxia directly affects the activities of contractile SMCs in the initial stage of AAA. Time-dependent pathological analysis clarified the cascade of AAA-related factors. These findings provide clues for understanding complicated multistage pathologies in AAA.

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Ovariectomy increases the incidence and diameter of abdominal aortic aneurysm in a hypoperfusion-induced abdominal aortic aneurysm animal model

Cited by 9 publications

References 34 publications

Ovariectomy Causes Degeneration of Perivascular Adipose Tissue

Ovariectomy Causes Degeneration of Perivascular Adipose Tissue

A Novel Hypothesis: A Role for Follicle Stimulating Hormone in Abdominal Aortic Aneurysm Development in Postmenopausal Women

Time-Dependent Pathological Changes in Hypoperfusion-Induced Abdominal Aortic Aneurysm

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