Circulating miR-29b decrease in response to sarcopenia in patients with cardiovascular risk factors in older Chinese

Abstract

Introduction: Sarcopenia is a clinical syndrome characterized by a progressive and extensive decline in skeletal muscle mass, muscle strength, and function. Sarcopenia and cardiovascular diseases (CVDs) can coexist, which further decreases the quality of life of patients, and increases the mortality rate. MicroRNAs (miRNAs) are unique posttranscriptional regulators of gene expression whose function in aging-related sarcopenia and CVDs has recently begun to unravel. The aim of the present study is to investigate the relationship between sarcopenia and cardiovascular risk factors (CVRF) in the Chinese elderly and describe the circulating miRNAs in sarcopenia patients with the intention of identifying novel diagnostic and therapeutic tools.

Methods: The well-established CVRF of diabetes, hypertension, and dyslipidemia were assessed. Multiple logistic regression analyses and linear regressions were used to evaluate the components of CVRF and the number of CVRF in elderly patients with sarcopenia. Moreover, we used real-time RT-PCR to measure the abundance of the CVRF-related miRNAs in the plasma of a cohort of 93 control and sarcopenia individuals, including miR-29b, miR-181a, and miR-494.

Results: We found that CVRF was associated with a high prevalence of sarcopenia in elderly Chinese populations After adjusting for potential confounders. Furthermore, hypertension and dyslipidemia, but not diabetes, were found to be significantly associated with sarcopenia. A linear increase in the prevalence of sarcopenia was found to be associated with the number of CVRF components in the elderly population. We found that plasma miR-29b levels were significantly down-regulated in response to sarcopenia in the elderly with CVRF. In particular, there was a remarkable correlation between miR-29b and appendicular skeletal muscle mass (ASM)/height2. Collectively, knowledge of CVRF, particularly hypertension and dyslipidemia, may help predict the risk of sarcopenia in the elderly. Our data also show that circulating miR-29b can be considered as possible biomarkers for sarcopenia, which may also be used in the CVD assessment of these patients.

Discussion: We found that the prevalence of sarcopenia was significantly proportional to the number of CVRF components. In particular, hypertension and dyslipidemia were significantly associated with a higher risk of sarcopenia in the adjusted models. Moreover, our study has been proven that c-miRNAs may be considered as possible biomarkers for sarcopenia as a new diagnostic tool to monitor response to treatment. There is also a pressing need for further research on sarcopenia and CVRF to understand their relationship and mechanism. These can provide more evidence to develop potential interventions to improve clinical outcomes.

Keywords: CVRF; biomarker; circulating microRNAs; elderly; sarcopenia.

FIGURE 1

Flow diagram of this study.

FIGURE 2

Changes in circulating microRNAs in response to sarcopenia in the elderly. The expression level of miRNAs was normalized using spike-in cel-miR-39; unpaired T-test was used for these data; *compared to non-sarcopenia of the elderly; *P < 0.05, **P < 0.01; n = 20.

FIGURE 3

CVRF-associated circulating miR-29b decrease in response to sarcopenia in the elderly. The expression level of miRNAs was normalized using spike-in cel-miR-39; unpaired T-test was used for these data; *compared to non-sarcopenia of the elderly; *P < 0.05; n = 73.

FIGURE 4

Correlation analysis between the changes of miR-29b and appendicular skeletal muscle mass (ASM)/Height² (kg/m²), handgrip strength (kg), and 4-m velocity (m/s). The correlation between the changes of miR-29b and the diagnostic indicators of sarcopenia (ASM/Height2, handgrip strength, and 4-m velocity) in sarcopenic and non-sarcopenic subjects (A). Pearson’s method was used for correlation analyses; *P < 0.05; n = 186. The correlation analysis of miR-29b with these indicators in male subjects (B). Pearson’s method was used for correlation analyses; *P < 0.05; n = 67. The correlation analysis of miR-29b with these indicators in female subjects (C). Pearson’s method was used for correlation analyses; *P < 0.05; n = 119.

FIGURE 5

Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of miR-29b, ASM/height2, and combine miR-29b with ASM/height2 for sarcopenia in the elderly; n = 186.