Zhang, Xiao
(2022)
Isoflavones, equol producing status, and atherosclerosis in Japanese men in Japan.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
Coronary heart disease (CHD) is the leading cause of morbidity and mortality worldwide. Soy is a potential nutritional source for preventing CHD and is a standard part of the traditional Asian diet. The main components of soy that may exert cardioprotective effects are soy isoflavones (ISFs). The predominant ISFs, daidzein, and genistein are structurally similar to estradiol and mimic some effects of estrogen. Estradiol exerts its biological action by binding both estrogen receptor α (ERα) expressed in reproductive, central nervous, cardiovascular and other systems and estrogen receptor β (ERβ) expressed in cardiovascular, central nervous and other systems. ISFs, however, preferentially bind to ERβ. ISFs may reduce CHD risk by reducing inflammation and oxidation; the latter may prevent the oxidative damage to low-density lipoprotein (LDL) that contributes to atherogenesis.
Although there are clear cardiovascular benefits of ISFs in preclinical studies, evidence in humans is conflicting. Furthermore, ISFs have very small or no effects on traditional CVD risk factors. A growing hypothesis is that the ability of humans to metabolize daidzein to equol may contribute to the cardioprotective effects of ISFs. Cell culture and preclinical studies show that equol has a greater affinity for ERβ than its precursor daidzein, a longer half-life, greater bioavailability than daidzein and genistein, and more potent antioxidant activity than any other ISFs. Therefore, equol may be more cardioprotective than ISFs.
The mechanistic model of action of equol on atherosclerosis is not completely understood. Investigation of the effects of equol has primarily been conducted in the in vitro assays and preclinical studies and lacks a sturdy conclusion. In addition, very few studies have explored the association between equol-producing status and atherosclerosis in humans. In this dissertation, I first conducted a systematic review summarizing the current knowledge about the mechanisms underlying the potential cardioprotective effect of equol on inflammation, oxidation, and endothelial function. I then performed two cross-sectional analyses to delineate the link between equol producing status and aortic calcification in Japanese, a population being widely acknowledged to have a high prevalence of equol-producers.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
|
| Date: |
4 January 2022 |
| Date Type: |
Publication |
| Defense Date: |
2 December 2021 |
| Approval Date: |
4 January 2022 |
| Submission Date: |
10 December 2021 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Number of Pages: |
168 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Public Health > Epidemiology |
| Degree: |
PhD - Doctor of Philosophy |
| Thesis Type: |
Doctoral Dissertation |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
Atherosclerosis, isoflavone, equol, Japan |
| Date Deposited: |
04 Jan 2022 15:14 |
| Last Modified: |
04 Jan 2022 15:14 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/42061 |
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