MicroRNA-30 regulates left ventricular hypertrophy in chronic kidney disease
Jingfu Bao, Yinghui Lu, Qinying She, Weijuan Dou, Rong Tang, Xiaodong Xu, Mingchao Zhang, Ling Zhu, Qing Zhou, Hui Li, Guohua Zhou, Zhongzhou Yang, Shaolin Shi, Zhihong Liu, Chunxia Zheng
Jingfu Bao, Yinghui Lu, Qinying She, Weijuan Dou, Rong Tang, Xiaodong Xu, Mingchao Zhang, Ling Zhu, Qing Zhou, Hui Li, Guohua Zhou, Zhongzhou Yang, Shaolin Shi, Zhihong Liu, Chunxia Zheng
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Research Article Cardiology Nephrology

MicroRNA-30 regulates left ventricular hypertrophy in chronic kidney disease

Abstract

Left ventricular hypertrophy (LVH) is a primary feature of cardiovascular complications in patients with chronic kidney disease (CKD). miRNA-30 is an important posttranscriptional regulator of LVH, but it is unknown whether miRNA-30 participates in the process of CKD-induced LVH. In the present study, we found that CKD not only resulted in LVH but also suppressed miRNA-30 expression in the myocardium. Rescue of cardiomyocyte-specific miRNA-30 attenuated LVH in CKD rats without altering CKD progression. Importantly, in vivo and in vitro knockdown of miRNA-30 in cardiomyocytes led to cardiomyocyte hypertrophy by upregulating the calcineurin signaling directly. Furthermore, CKD-related detrimental factors, such as fibroblast growth factor-23, uremic toxin, angiotensin II, and transforming growth factor–β, suppressed cardiac miRNA-30 expression, while miRNA-30 supplementation blunted cardiomyocyte hypertrophy induced by such factors. These results uncover a potentially novel mechanism of CKD-induced LVH and provide a potential therapeutic target for CKD patients with LVH.

Authors

Jingfu Bao, Yinghui Lu, Qinying She, Weijuan Dou, Rong Tang, Xiaodong Xu, Mingchao Zhang, Ling Zhu, Qing Zhou, Hui Li, Guohua Zhou, Zhongzhou Yang, Shaolin Shi, Zhihong Liu, Chunxia Zheng

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Figure 4

miR-30 knockdown in cardiomyocytes induces LVH.

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miR-30 knockdown in cardiomyocytes induces LVH. (A) Representative echoc...
(A) Representative echocardiogram, gross (original magnification, ×8; scale bar: 500 μm) and sagittal sections of the heart (hematoxylin and eosin staining; original magnification, ×8; scale bar: 500 μm), and WGA (original magnification, ×400; scale bar: 50 nm) and Masson staining of left ventricle (original magnification, ×400; scale bar: 50 nm). (B and C) IVS; d and relative wall thickness are significantly increased in 30SP mice. **P < 0.01 compared with values for the control (ctrl), by 2-tailed, unpaired Student’s t test. Data are shown as mean ± SD. n = 5 mice per group. (D) LVID; d is reduced in 30SP mice. **P < 0.01 compared with values for the ctrl, by 2-tailed, unpaired Student’s t test. Data are shown as mean ± SD. n = 5 mice per group. (E) No significant difference in ejection fractions between ctrl and 30SP mice. Compared with values for the ctrl, by 2-tailed, unpaired Student’s t test. Data are shown as mean ± SD. n = 5 mice per group. (F–H) 30SP mice manifest obvious increases in the ratios of heart weight to tibial length, LV weight to tibial length, and LV weight to heart weight. **P < 0.01 compared with values for the ctrl, by 2-tailed, unpaired Student’s t test. Data are shown as mean ± SD. n = 5 mice per group. (I) An increased cross-sectional area of cardiomyocytes in 30SP mice. **P < 0.01 compared with values for the ctrl, by 2-tailed, unpaired Student’s t test. Data are shown as median and quartiles, as well as the minimum and maximum values of the distribution. n = 300 cells per group.