ABSTRACT
BACKGROUND: Acylcarnitine is an intermediate product of fatty acid oxidation. It is reported to be closely associated with the occurrence of diabetic cardiomyopathy (DCM). However, the mechanism of acylcarnitine affecting myocardial disorders is yet to be explored. This current research explores the different chain lengths of acylcarnitines as biomarkers for the early diagnosis of DCM and the mechanism of acylcarnitines for the development of DCM in-vitro. METHODS: In a retrospective non-interventional study, 50 simple type 2 diabetes mellitus patients and 50 DCM patients were recruited. Plasma samples from both groups were analyzed by high throughput metabolomics and cluster heat map using mass spectrometry. Principal component analysis was used to compare the changes occurring in the studied 25 acylcarnitines. Multivariable binary logistic regression was used to analyze the odds ratio of each group for factors and the 95% confidence interval in DCM. Myristoylcarnitine (C14) exogenous intervention was given to H9c2 cells to verify the expression of lipid metabolism-related protein, inflammation-related protein expression, apoptosis-related protein expression, and cardiomyocyte hypertrophy and fibrosis-related protein expression. RESULTS: Factor 1 (C14, lauroylcarnitine, tetradecanoyldiacylcarnitine, 3-hydroxyl-tetradecanoylcarnitine, arachidic carnitine, octadecanoylcarnitine, 3-hydroxypalmitoleylcarnitine) and factor 4 (octanoylcarnitine, hexanoylcarnitine, decanoylcarnitine) were positively correlated with the risk of DCM. Exogenous C14 supplementation to cardiomyocytes led to increased lipid deposition in cardiomyocytes along with the obstacles in adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) signaling pathways and affecting fatty acid oxidation. This further caused myocardial lipotoxicity, ultimately leading to cardiomyocyte hypertrophy, fibrotic remodeling, and increased apoptosis. However, this effect was mitigated by the AMPK agonist acadesine. CONCLUSIONS: The increased plasma levels in medium and long-chain acylcarnitine extracted from factors 1 and 4 are closely related to the risk of DCM, indicating that these factors can be an important tool for DCM risk assessment. C14 supplementation associated lipid accumulation by inhibiting the AMPK/ACC/CPT1 signaling pathway, aggravated myocardial lipotoxicity, increased apoptosis apart from cardiomyocyte hypertrophy and fibrosis were alleviated by the acadesine.
Subject(s)
Carnitine/analogs & derivatives , Diabetes Mellitus, Type 2/complications , Diabetic Cardiomyopathies/metabolism , Lipid Metabolism , Adult , Aminoimidazole Carboxamide/analogs & derivatives , Aminoimidazole Carboxamide/pharmacology , Animals , Biomarkers/blood , Carnitine/blood , Carnitine/chemistry , Carnitine/pharmacology , Cell Line , Diabetes Mellitus, Type 2/metabolism , Female , Humans , Lipid Metabolism/drug effects , Male , Mass Spectrometry , Middle Aged , Myoblasts, Cardiac/drug effects , Myoblasts, Cardiac/metabolism , Myristic Acids/pharmacology , Rats , Retrospective Studies , Ribonucleosides/pharmacology , Risk FactorsABSTRACT
OBJECTIVE: To compare therapeutic effects of acupuncture at lateral cervical Jiaji and at traditional Jiaji points on cervical spondylosis of vertebroarterial type. METHODS: Seventy-two cases of vertebroarterial type cervical spondylosis were randomly divided into a needling lateral cervical Jiaji group (n=40) and a traditional Jiaji group (n=32). After 2 courses, therapeutic effects were evaluated and ultrasound Doppler's detection of skull was conducted. RESULTS: The therapeutic effect in the lateral cervical Jiaji group was better than that in the traditional Jiaji group (P < 0.05); And there was a significant or very significant difference between the two groups in the velocity of blood flow and the index of vascular pulsation (P < 0.05 or P < 0.01). CONCLUSION: The results of acupuncture at lateral cervical Jiaji points is better than that of acupuncture at traditional Jiaji points for treatment of cervical spondylosis of vertebroarterial type.