Circulating Level of miR-378 Predicts Left Ventricular Hypertrophy in Patients with Aortic Stenosis

Cui

Journal Cellular Physiology

et al. 2018

Doxorubicin (Dox) is a highly effective antitumor antibiotic, however myocardial toxicity severely limits its use clinically. The pathogenesis of doxorubicin‐induced cardiomyopathy is unclear. In Dox cardiomyopathy mice, there is a decline in cardiac function, a change in myocardial pathology and a reduction in miR378* expression. Expression changes in calumenin, an endoplasmic reticulum stress (ERS) chaperone protein and pathway factor, as well as apoptosis, were observed in cardiomyocytes after doxorubicin‐induced injury. However, miR378* increased calumenin expression, eased ERS, and reduced cardiomyocyte apoptosis, while, silencing miR378* reduced calumenin expression, aggravated ERS, and increased cardiomyocyte apoptosis. The above results indicate that miR378* alleviates ERS and inhibits the activation of the ERS‐mediated apoptosis signaling pathway in cardiomyocytes via regulating calumenin expression, thereby reducing cardiomyocyte apoptosis after doxorubicin‐induced injury. Increasing miR378* expression may be a new way to improve cardiac function and quality of life in patients with Dox cardiomyopathy.

Section: Discussionmentioning

confidence: 99%

“…Myocardial cell apoptosis is involved in many cardiovascular diseases (Chen et al, 2014;Fang et al, 2012). In this study, the number of Doxinjured myocardium cells that underwent apoptosis increased significantly and miR378* significantly reduced the apoptosis number of Dox-injured cardiomyocytes.…”

Section: Mir378* Inhibited Dox-induced Er Stress By Calumeninmentioning

confidence: 99%

Protective effect of miR378* on doxorubicin‐induced cardiomyocyte injury via calumenin

Cui

Journal Cellular Physiology

et al. 2018

Molecular Medicine Reports

“…The overexpression of miR-378 attenuates high glucose-suppressed osteogenic differentiation through targeting caspase 3 and activating the phosphoinositide 3-kinase/Akt signaling pathway (31). Circulating levels of miR-378 predicts left ventricular hypertrophy in patients with aortic stenosis (32). miRNA-378 controls classical brown fat expansion to counteract obesity (33).…”

Section: Discussionmentioning

confidence: 99%

Identification of serum miRNAs differentially expressed in human epilepsy at seizure onset and post-seizure

Sun¹,

Cheng²,

Liu³

et al. 2016

MicroRNAs (miRNAs) function as potential novel biomarkers for disease detection due to their marked stability in the blood and the characteristics of their expression profile in several diseases. In the present study, microarray‑based serum miRNA profiling was performed on serum obtained from three patients with epilepsy at diagnosis and from three healthy individuals as controls. This was followed by reverse transcription‑quantitative polymerase chain reaction analysis in a separate cohort of 35 health volunteers and 90 patients with epilepsy. The correlations between miRNAs and clinical parameters were analyzed. The array results showed that 15 miRNAs were overexpressed and 10 miRNAs were underexpressed (>2‑fold) in the patients with epilepsy. In addition, four miRNAs, including miR‑30a, miR‑378, miR‑106b and miR‑15a were found to be overexpressed in the serum of patients at seizure onset, compared with post‑seizure. When the patients were at seizure onset, the expression of miR‑30a was positively associated with seizure frequency. No significant differences were found between miR‑30a and gender, age or number of years following diagnosis. The expression levels of miR‑378, miR‑106b and mir‑15a were not associated with the clinical parameters in the patients with seizures. Calcium/calmodulin‑dependent protein kinase type IV was a target of miR‑30a, and its expression was increased following seizure and was negatively correlated with miR‑30a in the patients with epilepsy. The present study provided the first evidence, to the best of our knowledge, that the expression levels of miR‑378, miR‑30a, miR‑106b and miR‑15a were enhanced in epileptic patients with seizures. miR-30a may be useful for prognostic prediction in epilepsy.

“…Emerging blood biomarkers, such high-sensitivity cardiac troponin 194;195 , growth/differentiation factor 15, soluble interleukin-1 receptor-like 1 (also called protein ST2) and micro RNAs 196–198 , might be helpful to detect subclinical and/or irreversible myocardial dysfunction but their incremental value beyond already established clinical, echocardiographic, tomographic and blood biomarkers is yet to be demonstrated.…”

Section: Diagnosis Screening and Preventionmentioning

confidence: 99%

Calcific aortic stenosis

Lindman

Clavel

Mathieu

et al. 2016

Nat Rev Dis Primers

686

559

Calcific aortic stenosis (AS), the most prevalent heart valve disorder in developed countries,, is characterized by progressive fibro-calcific remodelling and thickening of the aortic valve leaflets that evolve over years to cause severe obstruction to cardiac outflow. In developed countries, AS is the second-most frequent cardiovascular disease after coronary artery disease and systemic arterial hypertension with a prevalence of 0.4% in the general population and 1.7% in the population >65 years old. Congenital abnormality (bicuspid valve) and older age are powerful risk factors for calcific AS. Metabolic syndrome and an elevated plasma level of lipoprotein(a) have also been associated with increased risk of calcific AS. The pathobiology of calcific AS is complex and involves genetic factors, lipoprotein deposition and oxidation, chronic inflammation, osteoblastic transition of cardiac valve interstitial cells and active leaflet calcification Although no pharmacotherapy has proven to be effective in reducing the progression of AS, promising therapeutic targets include lipoprotein(a), the renin-angiotensin system, tumor necrosis factor ligand superfamily member 11 (also called receptor activator of NF-κB ligand (RANKL)) and ectonucleotidases. Currently, aortic valve replacement (AVR) remains the only effective treatment for severe AS. The diagnosis and staging of AS are based on the assessment of stenosis severity and left ventricular systolic function by Doppler echocardiography and the presence of symptoms. The introduction of transcatheter AVR in the past decade has been a transformative innovation for patients at high or extreme-high risk for surgical AVR and this new technology might extend to lower-risk patients in the near future.