Cardiac hypertrophy and decreased high-density lipoprotein cholesterol in Lrig3-deficient mice
Cardiac hypertrophy and decreased high-density lipoprotein cholesterol in Lrig3-deficient mice
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DOI：
10.1152/ajpregu.00309.2015
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发表时间：
2016-06-01
影响因子：
2.8
通讯作者：
Hedman, Hakan
中科院分区：
文献类型：
--
作者：
Hellstrom, Martin;Ericsson, Madelene;Hedman, Hakan
遗传因素会增加心血管疾病的风险。最近，大规模的全基因组人群研究显示，LRIG 3附近的基因座与心力衰竭和血浆高密度脂蛋白（HDL）胆固醇水平之间存在关联。在这里，我们在小鼠中消融Lrig 3，并研究Lrig 3对心脏功能和血脂水平的重要性。采用定量逆转录-聚合酶链反应（RT-PCR）分析野生型和Lrig 3缺陷小鼠心脏中Lrig 3的表达。此外，还评价了分子、生理和功能参数，如器官重量、心率、血压、心脏结构和功能、心脏中的基因表达以及血浆胰岛素、葡萄糖和脂质水平。Lrig 3缺陷小鼠比野生型小鼠小，但在其他方面表现正常。Lrig 3在成年小鼠心脏中以可检测但相对较低的水平表达。在9月龄时，自由采食Lrig 3缺陷小鼠的胰岛素水平低于野生型小鼠。在12月龄时，Lrig 3缺陷小鼠表现出血压升高，并且Lrig 3缺陷雌性小鼠表现出心脏肥大的迹象，如通过超声心动图、心脏与体重比和心脏肥大标记基因Nppa的表达所评估的。此外，Lrig 3缺陷小鼠的血浆HDL胆固醇和游离甘油减少。这些在小鼠中的发现补充了人类流行病学结果，并表明Lrig 3可能影响小鼠和人类的心脏功能和血浆脂质水平。
Genetic factors confer risk for cardiovascular disease. Recently, large genome-wide population studies have shown associations between genomic loci close to LRIG3 and heart failure and plasma high-density lipoprotein (HDL) cholesterol level. Here, we ablated Lrig3 in mice and investigated the importance of Lrig3 for heart function and plasma lipid levels. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to analyze Lrig3 expression in the hearts of wild-type and Lrig3-deficient mice. In addition, molecular, physiological, and functional parameters such as organ weights, heart rate, blood pressure, heart structure and function, gene expression in the heart, and plasma insulin, glucose, and lipid levels were evaluated. The Lrig3-deficient mice were smaller than the wild-type mice but otherwise appeared grossly normal. Lrig3 was expressed at detectable but relatively low levels in adult mouse hearts. At 9 mo of age, ad libitum-fed Lrig3-deficient mice had lower insulin levels than wildtype mice. At 12 mo of age, Lrig3-deficient mice exhibited increased blood pressure, and the Lrig3-deficient female mice displayed signs of cardiac hypertrophy as assessed by echocardiography, heart-to-body weight ratio, and expression of the cardiac hypertrophy marker gene Nppa. Additionally, Lrig3-deficient mice had reduced plasma HDL cholesterol and free glycerol. These findings in mice complement the human epidemiological results and suggest that Lrig3 may influence heart function and plasma lipid levels in mice and humans.