Choose Your Maternal DNA Wisely: Intrinsic Exercise Capacity and Mitochondrial Genome Influence Vascular Function in Rats.
Choose Your Maternal DNA Wisely: Intrinsic Exercise Capacity and Mitochondrial Genome Influence Vascular Function in Rats.
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DOI：
10.1093/function/zqaa039
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Robinson AT
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文献类型：
--
作者：
Robinson AT
“明智地选择你的父母”是英国哲学家伯特兰·罗素创造的一句流行格言，经常在讨论社会经济地位和基因对疾病风险的贡献等问题时使用。当谈到血管功能，心血管疾病风险的预测指标，Roy等人最近在Function上的研究。1引申出这句格言：“明智地选择我们的母体线粒体DNA。”这项研究描述了低跑步能力(LCR)和高跑步能力(HCR)大鼠的血管功能。有氧运动是预防和治疗心血管和代谢性疾病状态的一种积极的健康行为。有氧运动训练通常会改善心肺功能(CRF)，2但固有能力和可训练性的遗传倾向导致了很大的变异性。3重要的是，CRF是心血管和全因死亡率的预测因子。4此外，阻力动脉功能障碍先于高血压和心血管疾病造成的终末器官损害。5因此，作者试图确定CRF是否影响阻力动脉结构和功能、心功能、血管周围脂肪组织(PVAT)和血管细胞的生物能量谱。此外，研究人员试图确定与内在运动能力相关的遗传线粒体基因组是否也独立影响血管生理学。研究人员研究了人工选择(在家庭内)具有内在有氧耐力跑能力的大鼠，以产生LCR和HCR雄性大鼠。3如前所述，6作者还产生了共生品系，其中LCR雄性啮齿动物与雌性HCR啮齿动物的线粒体DNA(MtDNA)杂交(LCR-mtHCR)，反之亦然(HCR-mtLCR)。具体地说，通过近亲交配，将Hcr雌性后代与雄性LCR(或正反交)回交，这种回交过程在几个世代中重复，产生LCR-mtHCR和Hcr-mtLCR。研究人员进行了超声心动图检查以评估心功能和左心室重量，线缆和压力肌图检查以评估动脉血管扩张功能(有无PVAT)和力学，PVAT的宏观组织成像，以及血管平滑肌细胞(VSMCs)的生物能量分析。与HCR相比，LCR大鼠具有更高的体质量、附睾脂质量和血压。在心脏测量方面，HCR大鼠的左心室重量高于LCR大鼠(见图1)。与LCR相比，HCR大鼠表现出较低的相对室壁厚度和面积变化分数(收缩功能的替代指标)，但在心输出量、周向纤维缩短速度或心肌收缩能力的多项指标上没有观察到差异。有趣的是，线粒体交换增加了LCR(即LCR-mtHCR)的左心室质量，但降低了HCR-mtLCR的左心室质量和心功能的几个指数。主要的发现是，与HCR相比，LCR大鼠肠系膜阻力动脉的内皮依赖性(乙酰胆碱)和非内皮依赖性(硝普钠)血管扩张较低。线粒体交换挽救了LCR(LCR-mtHCR)的内皮依赖性和非内皮依赖性血管扩张(LCR-mtHCR)，但并未降低HCR-mtLCR的血管功能。使用肠系膜小动脉，并用腔内压力曲线绘制内腔和外径，作者揭示了
“Choose your parents wisely” is a popular adage coined by the British Philosopher Bertrand Russell, and often used when discussing issues such as socioeconomic position and genetic contributions to disease risk. When it comes to vascular function, a predictor of cardiovascular disease risk, the recent study in Function by Roy et al. 1 extends the adage to “choose our maternal mitochondrial DNA wisely.” The study characterized vascular function in rats with a low capacity for running (LCR) and high capacity for running (HCR). Aerobic exercise is a positive health behavior for the prevention and treatment of cardiovascular and metabolic disease states. Aerobic exercise training generally leads to improved cardiorespiratory fitness (CRF), 2 but genetic predispositions for intrinsic capacity and trainability lead to substantial variability. 3 Importantly, CRF is a predictor of cardiovascular and all-cause mortality. 4 Moreover, resistance artery dysfunction precedes end-organ damage from hypertension and cardiovascular disease. 5 Thus, the authors sought to determine whether CRF influences resistance artery structure and function, cardiac function, perivascular adipose tissue (PVAT), and bioenergetic profiling in vascular cells. Moreover, the researchers sought to determine whether the inherited mitochondrial genome associated with intrinsic exercise capacity also independently influences vascular physiology. The investigators studied rats artificially selected (withinfamily) for intrinsic aerobic endurance running capacity to generate LCR and HCR male rats. 3 As previously described, 6 the authors also generated conplastic strains, whereby LCR male rodents were bred with mitochondrial DNA (mtDNA) of female HCR rodents (LCR-mtHCR) and vice versa (HCR-mtLCR). Specifically, HCR female offspring were backcrossed with male LCR (or the reciprocal) via inbreeding, and this backcross procedure was repeated over several generations to generate the LCR-mtHCR and HCR-mtLCR. The investigators performed echocardiography to assess cardiac function and left ventricular mass, wire, and pressure myography to assess arterial vasodilatory function (with and without PVAT) and mechanics, macroscopic tissue imaging of PVAT, and bioenergetic assays with vascular smooth muscle cells (VSMCs). Compared to HCR, LCR rats had higher body mass, epididymal fat mass, and blood pressure. Regarding cardiac measures, HCR rats presented higher left ventricular mass than LCR rats (see Figure 1). Compared to LCR, HCR rats exhibited lower relative ventricular wall thickness and fractional area change, a surrogate of systolic function, but no differences were observed for multiple measures of cardiac output, velocity of circumferential fiber shortening, or myocardial contractility. Interestingly, mitochondrial swap increased left ventricular mass in LCR (ie," in LCR-mtHCR) but decreased left ventricular mass and several indices of cardiac performance in HCR-mtLCR relative to HCR. The key findings were that compared to HCR, LCR rats presented with lower endothelium-dependent (acetylcholine) and endothelium-independent (sodium nitroprusside) vasodilation in mesenteric resistance arteries. Mitochondrial swap rescued endothelium-dependent and endothelium-independent vasodilation in LCR (" in LCR-mtHCR), however, it did not reduce vascular function in HCR-mtLCR. Using mesenteric arterioles and plotting internal lumen and external diameters with intraluminal pressure curves, the authors revealed that the
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DOI：
10.1161/atvbaha.118.311229
发表时间：
2018-09
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Brown IAM;Diederich L;Good ME;DeLalio LJ;Murphy SA;Cortese-Krott MM;Hall JL;Le TH;Isakson BE
通讯作者：
Isakson BE
DOI：
10.1093/function/zqaa029
发表时间：
2021
期刊：
Function (Oxford, England)
影响因子：
--
作者：
Roy S;Edwards JM;Tomcho JC;Schreckenberger Z;Bearss NR;Zhang Y;Morgan EE;Cheng X;Spegele AC;Vijay-Kumar M;McCarthy CG;Koch LG;Joe B;Wenceslau CF
通讯作者：
Wenceslau CF
影响因子：
2.7
作者：
Bouchard, Claude
通讯作者：
Bouchard, Claude
影响因子：
24
作者：
Imboden, Mary T.;Harber, Matthew P.;Kaminsky, Leonard A.
通讯作者：
Kaminsky, Leonard A.
影响因子：
4.6
作者：
Zhang, Youjie;Kumarasamy, Sivarajan;Joe, Bina
通讯作者：
Joe, Bina