Female and male mice have differential longterm cardiorenal outcomes following a matched degree of ischemia-reperfusion acute kidney injury.
Female and male mice have differential longterm cardiorenal outcomes following a matched degree of ischemia-reperfusion acute kidney injury.
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DOI：
10.1038/s41598-021-04701-x
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发表时间：
2022-01-12
影响因子：
4.6
通讯作者：
Faubel S
中科院分区：
文献类型：
--
作者：
Soranno DE;Baker P 2nd;Kirkbride-Romeo L;Wennersten SA;Ding K;Keith B;Cavasin MA;Altmann C;Bagchi RA;Haefner KR;Montford J;Gist KM;Vergnes L;Reue K;He Z;Elajaili H;Okamura K;Nozik E;McKinsey TA;Faubel S
急性肾损伤（阿基）在患者中很常见，会引起全身性后遗症，并使患者易患长期心血管疾病。迄今为止，阿基对心血管结局影响的研究仅在雄性小鼠中进行。我们最近证明，与假手术相比，阿基后1年，雄性小鼠出现舒张功能障碍、高血压和心脏ATP水平降低。女性对阿基后长期心脏结局的影响尚不清楚。因此，我们使用阿基严重程度相似的模型检查了雌性C57 BL/6小鼠单次双侧肾缺血-再灌注损伤后1年的心肾结局，并与最近发表的雄性队列同时进行。为了匹配雄性和雌性小鼠之间阿基的严重程度，雌性小鼠接受34分钟的缺血时间，而雄性小鼠接受25分钟。在整个1年研究期间进行了系列肾功能、超声心动图和血压评估。在1年时评价肾组织学、心脏和血浆代谢组学以及心脏和肾脏中的线粒体功能。在整个1年研究期间，雄性和雌性小鼠之间测量的肾小球滤过率（GFR）相似。阿基后一年，雌性小鼠的舒张功能、血压正常，心脏ATP水平保持不变。与雄性动物相比，雌性动物的心脏和血浆中精氨酸代谢和氨基酸相关能量产生以及血浆中谷胱甘肽的途径富集。与雄性相比，无论阿基或假手术，电子传递链复合物I中的心脏线粒体呼吸均显示雌性线粒体功能改善。这是第一项研究阿基对雌性小鼠的长期心脏影响，并表明存在重要的性别相关心肾差异。女性在阿基后心血管结局中的作用值得进一步研究。
Acute kidney injury (AKI) is common in patients, causes systemic sequelae, and predisposes patients to long-term cardiovascular disease. To date, studies of the effects of AKI on cardiovascular outcomes have only been performed in male mice. We recently demonstrated that male mice developed diastolic dysfunction, hypertension and reduced cardiac ATP levels versus sham 1 year after AKI. The effects of female sex on long-term cardiac outcomes after AKI are unknown. Therefore, we examined the 1-year cardiorenal outcomes following a single episode of bilateral renal ischemia–reperfusion injury in female C57BL/6 mice using a model with similar severity of AKI and performed concomitantly to recently published male cohorts. To match the severity of AKI between male and female mice, females received 34 min of ischemia time compared to 25 min in males. Serial renal function, echocardiograms and blood pressure assessments were performed throughout the 1-year study. Renal histology, and cardiac and plasma metabolomics and mitochondrial function in the heart and kidney were evaluated at 1 year. Measured glomerular filtration rates (GFR) were similar between male and female mice throughout the 1-year study period. One year after AKI, female mice had preserved diastolic function, normal blood pressure, and preserved levels of cardiac ATP. Compared to males, females demonstrated pathway enrichment in arginine metabolism and amino acid related energy production in both the heart and plasma, and glutathione in the plasma. Cardiac mitochondrial respiration in Complex I of the electron transport chain demonstrated improved mitochondrial function in females compared to males, regardless of AKI or sham. This is the first study to examine the long-term cardiac effects of AKI on female mice and indicate that there are important sex-related cardiorenal differences. The role of female sex in cardiovascular outcomes after AKI merits further investigation.
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DOI：
10.1056/nejmoa1611391
发表时间：
2017-01-05
期刊：
The New England journal of medicine
影响因子：
--
作者：
Kaddourah A;Basu RK;Bagshaw SM;Goldstein SL;AWARE Investigators
通讯作者：
AWARE Investigators
DOI：
10.1161/atvbaha.116.307301
发表时间：
2017-05
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Arnold AP;Cassis LA;Eghbali M;Reue K;Sandberg K
通讯作者：
Sandberg K
影响因子：
17.1
作者：
Jeong MY;Lin YH;Wennersten SA;Demos-Davies KM;Cavasin MA;Mahaffey JH;Monzani V;Saripalli C;Mascagni P;Reece TB;Ambardekar AV;Granzier HL;Dinarello CA;McKinsey TA
通讯作者：
McKinsey TA
DOI：
10.1097/01.asn.0000064946.94590.46
发表时间：
2003-06-01
影响因子：
13.6
作者：
Kelly, KJ
通讯作者：
Kelly, KJ
影响因子：
2.6
作者：
Hegde A;Denburg MR;Glenn DA
通讯作者：
Glenn DA