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An Investigation into the Role of MicroRNAs in Myocardial Ischemia-reperfusion Injury in Late Pregnancy
An Investigation into the Role of MicroRNAs in Myocardial Ischemia-reperfusion Injury in Late Pregnancy
상세정보
- 자료유형
- 학위논문 서양
- 최종처리일시
- 20250211151510
- ISBN
- 9798382733364
- DDC
- 574
- 저자명
- Aryan, Laila.
- 서명/저자
- An Investigation into the Role of MicroRNAs in Myocardial Ischemia-reperfusion Injury in Late Pregnancy
- 발행사항
- [Sl] : University of California, Los Angeles, 2024
- 발행사항
- Ann Arbor : ProQuest Dissertations & Theses, 2024
- 형태사항
- 146 p
- 주기사항
- Source: Dissertations Abstracts International, Volume: 85-11, Section: B.
- 주기사항
- Advisor: Eghbali, Mansoureh.
- 학위논문주기
- Thesis (Ph.D.)--University of California, Los Angeles, 2024.
- 초록/해제
- 요약Maternal mortality remains high in the US and pregnancy-associated myocardial infarction accounts for over 20% of maternal cardiac deaths. The relative risk of myocardial infarction during pregnancy is approximately 3 to 4-fold higher than the rates of age-matched non-pregnant individuals in the reproductive age group. During myocardial infarction, ischemia restricts blood flow to the myocardium, necessitating timely reperfusion therapy to restore blood flow. However, reperfusion therapy can exacerbate tissue damage. Our lab has demonstrated that cardiac vulnerability to ischemia reperfusion injury drastically increases in late pregnancy, and one bolus of intralipid at reperfusion reduces the infarct size in late pregnant rats. However, the mechanisms underlying the higher vulnerability of late pregnancy to ischemia reperfusion injury and the cardioprotective role of intralipid are unknown. In Chapter 2, we employ a rat model to investigate the reasons behind the heightened susceptibility of the heart in late pregnancy to ischemia-reperfusion injury. We identify microRNA-98-5p, whose expression increases during late pregnancy upon ischemia reperfusion injury, and promotes cardiomyocyte apoptosis, mitochondrial oxidative stress, and inflammation via its targets Stat3 and Pgc-1α. In an in vivo late pregnant ischemia-reperfusion injury rat model, we show the therapeutic potential of microRNA-98-5p inhibition at the onset of reperfusion. In late pregnant patients with acute myocardial infarction, plasma microRNA-98-5p was significantly higher than healthy late pregnancy and it was correlated with troponin levels. In Chapter 3, we study the therapeutic role of intralipid in attenuating ischemia-reperfusion injury in a rat model of late pregnancy. We demonstrate that the protective effects of intralipid are mediated by microRNA-122-5p. MicroRNA-122-5p exhibits its protective effects in late pregnancy by mitigating cardiomyocyte apoptosis and oxidative stress through its target Pkm2. In humans, plasma microRNA-122-5p levels were lower in healthy late pregnant compared to healthy non-pregnant individuals and even lower in late pregnant patients with acute MI and negatively correlated with troponin levels. In an in vivo late pregnant ischemia-reperfusion injury rat model, we show the therapeutic potential of microRNA-122-5p overexpression at the onset of reperfusion.Taken together, this dissertation offers insights into the heightened susceptibility of late pregnancy to ischemia-reperfusion injury and the cardioprotective role of intralipid.
- 일반주제명
- Biology
- 일반주제명
- Cellular biology
- 일반주제명
- Physiology
- 일반주제명
- Obstetrics
- 키워드
- Heart attack
- 키워드
- Heart failure
- 키워드
- MicroRNA
- 키워드
- Pregnancy
- 기타저자
- University of California, Los Angeles Molec Cell & Integ Physiology 0568
- 기본자료저록
- Dissertations Abstracts International. 85-11B.
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
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■00520250211151510
■006m o d
■007cr#unu||||||||
■020 ▼a9798382733364
■035 ▼a(MiAaPQ)AAI31299631
■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a574
■1001 ▼aAryan, Laila.
■24513▼aAn Investigation into the Role of MicroRNAs in Myocardial Ischemia-reperfusion Injury in Late Pregnancy
■260 ▼a[Sl]▼bUniversity of California, Los Angeles▼c2024
■260 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2024
■300 ▼a146 p
■500 ▼aSource: Dissertations Abstracts International, Volume: 85-11, Section: B.
■500 ▼aAdvisor: Eghbali, Mansoureh.
■5021 ▼aThesis (Ph.D.)--University of California, Los Angeles, 2024.
■520 ▼aMaternal mortality remains high in the US and pregnancy-associated myocardial infarction accounts for over 20% of maternal cardiac deaths. The relative risk of myocardial infarction during pregnancy is approximately 3 to 4-fold higher than the rates of age-matched non-pregnant individuals in the reproductive age group. During myocardial infarction, ischemia restricts blood flow to the myocardium, necessitating timely reperfusion therapy to restore blood flow. However, reperfusion therapy can exacerbate tissue damage. Our lab has demonstrated that cardiac vulnerability to ischemia reperfusion injury drastically increases in late pregnancy, and one bolus of intralipid at reperfusion reduces the infarct size in late pregnant rats. However, the mechanisms underlying the higher vulnerability of late pregnancy to ischemia reperfusion injury and the cardioprotective role of intralipid are unknown. In Chapter 2, we employ a rat model to investigate the reasons behind the heightened susceptibility of the heart in late pregnancy to ischemia-reperfusion injury. We identify microRNA-98-5p, whose expression increases during late pregnancy upon ischemia reperfusion injury, and promotes cardiomyocyte apoptosis, mitochondrial oxidative stress, and inflammation via its targets Stat3 and Pgc-1α. In an in vivo late pregnant ischemia-reperfusion injury rat model, we show the therapeutic potential of microRNA-98-5p inhibition at the onset of reperfusion. In late pregnant patients with acute myocardial infarction, plasma microRNA-98-5p was significantly higher than healthy late pregnancy and it was correlated with troponin levels. In Chapter 3, we study the therapeutic role of intralipid in attenuating ischemia-reperfusion injury in a rat model of late pregnancy. We demonstrate that the protective effects of intralipid are mediated by microRNA-122-5p. MicroRNA-122-5p exhibits its protective effects in late pregnancy by mitigating cardiomyocyte apoptosis and oxidative stress through its target Pkm2. In humans, plasma microRNA-122-5p levels were lower in healthy late pregnant compared to healthy non-pregnant individuals and even lower in late pregnant patients with acute MI and negatively correlated with troponin levels. In an in vivo late pregnant ischemia-reperfusion injury rat model, we show the therapeutic potential of microRNA-122-5p overexpression at the onset of reperfusion.Taken together, this dissertation offers insights into the heightened susceptibility of late pregnancy to ischemia-reperfusion injury and the cardioprotective role of intralipid.
■590 ▼aSchool code: 0031.
■650 4▼aBiology
■650 4▼aCellular biology
■650 4▼aPhysiology
■650 4▼aObstetrics
■653 ▼aCardiovascular diseases
■653 ▼aHeart attack
■653 ▼aHeart failure
■653 ▼aMicroRNA
■653 ▼aMyocardial infarction
■653 ▼aPregnancy
■690 ▼a0306
■690 ▼a0379
■690 ▼a0380
■690 ▼a0719
■71020▼aUniversity of California, Los Angeles▼bMolec, Cell, & Integ Physiology 0568.
■7730 ▼tDissertations Abstracts International▼g85-11B.
■790 ▼a0031
■791 ▼aPh.D.
■792 ▼a2024
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17161982▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
