Programming of cardiac metabolism by miR-15b-5p, a miRNA released in cardiac extracellular vesicles following ischemia-reperfusion injury.
Programming of cardiac metabolism by miR-15b-5p, a miRNA released in cardiac extracellular vesicles following ischemia-reperfusion injury.
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DOI：
10.1016/j.molmet.2024.101875
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发表时间：
2024-02
影响因子：
8.1
通讯作者：
Ozanne SE
中科院分区：
文献类型：
--
作者：
Pantaleão LC;Loche E;Fernandez-Twinn DS;Dearden L;Córdova-Casanova A;Osmond C;Salonen MK;Kajantie E;Niu Y;de Almeida-Faria J;Thackray BD;Mikkola TM;Giussani DA;Murray AJ;Bushell M;Eriksson JG;Ozanne SE
我们研究了mirna在母亲肥胖引起的心血管疾病（CVD）发育过程中的潜在参与。研究人员测量了赫尔辛基出生队列（已知母亲体重指数）个体的血清miRNA，并使用小鼠模型来确定怀孕期间母亲肥胖和缺血再灌注对后代心脏miRNA表达和释放的影响。miR-15b-5p水平在BMI较高的母鼠所生的雄性血清和肥胖母鼠所生的成年小鼠的心脏中升高。在灌注小鼠心脏的离体模型中，我们证明心脏组织释放miR-15b-5p，并且一些释放的miR-15b-5p包含在小细胞外囊泡（ev）中。我们还证明，缺血/再灌注后暴露于母亲肥胖的心脏释放量更高。在体外过度表达miR-15b-5p导致线粒体外膜稳定性丧失，并抑制心肌细胞中的脂肪酸氧化。这些发现表明，miR-15-b可能在暴露于子宫内致肥环境后心脏代谢失调中发挥机制作用，并且缺血损伤后其在心脏ev中的释放可能是促进程序化心脏和外周组织之间器官间通信的新因素。肥胖母鼠后代的心脏更容易发生缺血再灌注损伤。在人类中，母体BMI升高与后代血清miR-15b升高相关。母亲肥胖导致小鼠后代心脏miRNA-15b表达增加。miR-15b-5p在体外调节心肌细胞代谢。miR-15b-5p基本从心脏释放，并在缺血时升高。
We investigated the potential involvement of miRNAs in the developmental programming of cardiovascular diseases (CVD) by maternal obesity. Serum miRNAs were measured in individuals from the Helsinki Birth Cohort (with known maternal body mass index), and a mouse model was used to determine causative effects of maternal obesity during pregnancy and ischemia-reperfusion on offspring cardiac miRNA expression and release. miR-15b-5p levels were increased in the sera of males born to mothers with higher BMI and in the hearts of adult mice born to obese dams. In an ex-vivo model of perfused mouse hearts, we demonstrated that cardiac tissue releases miR-15b-5p, and that some of the released miR-15b-5p was contained within small extracellular vesicles (EVs). We also demonstrated that release was higher from hearts exposed to maternal obesity following ischaemia/reperfusion. Over-expression of miR-15b-5p in vitro led to loss of outer mitochondrial membrane stability and to repressed fatty acid oxidation in cardiomyocytes. These findings suggest that miR-15-b could play a mechanistic role in the dysregulation of cardiac metabolism following exposure to an in utero obesogenic environment and that its release in cardiac EVs following ischaemic damage may be a novel factor contributing to inter-organ communication between the programmed heart and peripheral tissues. Hearts from offspring of obese dams are more vulnerable to ischemia-reperfusion damage. Increased maternal BMI is associated with increased offspring serum miR-15b in humans. Maternal obesity leads to increased cardiac miRNA-15b expression in mice offspring. miR-15b-5p regulates cardiomyocyte metabolism in vitro. miR-15b-5p is released from hearts basally and increased in response to ischemia.
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影响因子：
8.1
作者：
Fernandez-Twinn DS;Alfaradhi MZ;Martin-Gronert MS;Duque-Guimaraes DE;Piekarz A;Ferland-McCollough D;Bushell M;Ozanne SE
通讯作者：
Ozanne SE
影响因子：
12.4
作者：
通讯作者：
--
影响因子：
8.2
作者：
de Almeida-Faria J;Duque-Guimarães DE;Ong TP;Pantaleão LC;Carpenter AA;Loche E;Kusinski LC;Ashmore TJ;Antrobus R;Bushell M;Fernandez-Twinn DS;Ozanne SE
通讯作者：
Ozanne SE
DOI：
10.3724/sp.j.1263.2012.00028
发表时间：
2012-03
期刊：
Journal of geriatric cardiology : JGC
影响因子：
--
作者：
Liu LF;Liang Z;Lv ZR;Liu XH;Bai J;Chen J;Chen C;Wang Y
通讯作者：
Wang Y
影响因子：
8
作者：
Boney, CM;Verma, A;Vohr, BR
通讯作者：
Vohr, BR