Shuai Jiang1,2, Qian-Ru Ye1,3, Rong-Xia Zhen4, Juan-Niu Zhang5, Yi-Yi Zhang1, Xu Liu1, Jie Hou6. 1. Institute of Keshan Disease, Chinese Center for Endemic Disease Control, Harbin Medical University, Harbin, 150081, China. 2. Affiliated Hospital of Jilin Medical College, Jilin, 132013, China. 3. Hangzhou Center for Disease Control and Prevention, Hangzhou, 310021, China. 4. Sanya Institute of Technology, Sanya, 572022, China. 5. Inner Mongolia Autonomous Region Mental Health Center, Hohhot, 010010, China. 6. Institute of Keshan Disease, Chinese Center for Endemic Disease Control, Harbin Medical University, Harbin, 150081, China. houjie@ems.hrbmu.edu.cn.
Abstract
OBJECTIVE: Keshan disease (KD) is a mitochondrial cardiomyopathy. The present study explored the roles of peroxisome proliferator-activated receptor (PPAR)-γ coactivator-1α (PGC-1α), the key regulator of mitochondrial structure and function, and its coactivators in myocardial injury in chronic KD. Furthermore, the usefulness of these molecules in the diagnosis of chronic KD was assessed. METHODS: In the present case-control study, 43 patients with chronic KD and 30 healthy individuals living in KD endemic areas were included. The myocardial injury indicators and mRNA expression levels of PGC-1α, nuclear respiratory factor 1 (NRF1), PPARα, and estrogen-related receptor alpha (ERRα) in peripheral blood were examined. RESULTS: It was found that the levels of atrial natriuretic peptide, creatine kinase, and lactate dehydrogenase (LDH) were higher in patients with chronic KD, when compared to controls, while the level of bradykinin was lower. Furthermore, the PGC-1α, NRF1 and PPARα mRNA levels were higher in patients with KD. The area under the receiver operating characteristic curve and the optimal diagnostic threshold of LDH was 0.937 and 304.0 U/L, respectively. It is noteworthy that the area under the combined receiver operating characteristic curve was larger, when compared to that for LDH detection alone (Z=2.055, P=0.0399). The area under the curve for the "LDH+PPARα" combination was 0.984, with 96.7% sensitivity and 93.0% specificity. CONCLUSION: The combined detection of LDH and the expression of PPARα can be performed to diagnose the chronic KD.
OBJECTIVE: Keshan disease (KD) is a mitochondrial cardiomyopathy. The present study explored the roles of peroxisome proliferator-activated receptor (PPAR)-γ coactivator-1α (PGC-1α), the key regulator of mitochondrial structure and function, and its coactivators in myocardial injury in chronic KD. Furthermore, the usefulness of these molecules in the diagnosis of chronic KD was assessed. METHODS: In the present case-control study, 43 patients with chronic KD and 30 healthy individuals living in KD endemic areas were included. The myocardial injury indicators and mRNA expression levels of PGC-1α, nuclear respiratory factor 1 (NRF1), PPARα, and estrogen-related receptor alpha (ERRα) in peripheral blood were examined. RESULTS: It was found that the levels of atrial natriuretic peptide, creatine kinase, and lactate dehydrogenase (LDH) were higher in patients with chronic KD, when compared to controls, while the level of bradykinin was lower. Furthermore, the PGC-1α, NRF1 and PPARα mRNA levels were higher in patients with KD. The area under the receiver operating characteristic curve and the optimal diagnostic threshold of LDH was 0.937 and 304.0 U/L, respectively. It is noteworthy that the area under the combined receiver operating characteristic curve was larger, when compared to that for LDH detection alone (Z=2.055, P=0.0399). The area under the curve for the "LDH+PPARα" combination was 0.984, with 96.7% sensitivity and 93.0% specificity. CONCLUSION: The combined detection of LDH and the expression of PPARα can be performed to diagnose the chronic KD.