Cardiac fibrosis (CF) is regulated by multiple factors, including transforming growth factor beta 1 (TGF beta 1) and non-coding RNAs. Thrombospondin 1 (TSP1) is a physiologic regulator of TGF beta activation. Here, we performed microarray analyses on mRNAs and lncRNAs differentially-expressed in the CF and normal rat hearts. KEGG signaling annotation and GO enrichment analyses were performed to validate the roles of extracellular matrix (ECM) and TSP1-enhanced TGF beta activation in CF. The co-expression network between differentially-expressed lncRNAs and ECM-related factors was constructed to identify candidate lncRNAs and miRNAs. We found that lncRNA Homo sapiens ring finger protein 7 (lnc RNF7) was significantly correlated with TSP1 and ECM. Lnc RNF7 silence could attenuate isoproterenol (ISP)-induced CF in rat heart in vivo and in rat cardiac fibroblasts in vitro. Moreover, angiotensin II (Ang II) -induced CF in rat cardiac fibroblasts could also be attenuated by Lnc RNF7 silence. Furthermore, miR-543 could simultaneously target lnc RNF7 and 3' UTR of TSP1. Lnc RNF7 silence suppressed, while miR-543 inhibition promoted TSP1 protein and TGF beta activation, as well as ECM markers expression. The effects of lnc RNF7 silence was significantly reversed by miR-543 inhibition. In conclusion, CF progression might be regulated by lnc RNF7/miR-543 axis via TSP1-mediated TGF beta activation.

O simertinib, a third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKIs), is approved globally as the first-line treatment for patients with EGFR mutations (EGFRm: Ex19del/L858R) and T790M resistance mutations in advanced non-small cell lung cancer (NSCLC). [1-3] With its widespread use, the cardiotoxicity of osimertinib has been of great concern. According to the U.S. Food and Drug Administration Adverse Events Reporting System (FAERS), the main cardiac-related adverse events with EGFR-TKIs are heart failure, QT prolongation, atrial fibrillation, acute myocardial infarction and pericardial effusion, and osimertinib has a higher incidence of QT prolongation, heart failure and atrial fibrillation than other EGFR-TKIs. [4] As mentioned in its package insert, a decline in left ventricular ejection fraction (LVEF) of > 10% from baseline and to less than 50% of LVEF occurred in 3.2% of patients following osimertinib treatment in clinical trials, 0.8% of patients were found to have a heart rate corrected QT interval (QTc) of > 500 ms, and 3.1% of patients had a QTc increase from baseline of > 60 ms. No QTc-related arrhythmias were reported. [5] This is an 81-year-old male patient whose medical history is shown in Figure 1. Eight months ago, two nodules (LU-RADS class 4) in the left upper lung were revealed by CT scan at physical examination, located in the posterior apical segment and the lingual segment (Figure 2A). The patient presented with left-side chest pain and an electrocardiogram suggestive of lateral wall myocardial ischemia (Figure 2B). Accordingly, he underwent coronary angiography, the results of which showed 50% stenosis in the proximal segment of the left anterior descending bra

Our research was designed to figure out the influence and mechanism of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor on the improvement of elderly essential hypertension-induced vascular endothelial function impairment based on the JAK/STAT pathway. Eighty-six elderly patients with essential hypertension were randomized into a control group (oral Amlodipine Besylate Tablets) and an observation group (oral Amlodipine Besylate Tablets + HMG-CoA reductase inhibitor atorvastatin calcium). Patients in both groups were treated with the drug for 12 weeks. Blood pressure, serum levels of inflammatory factors, and vascular endothelial function indicators, and levels of blood lipids were measured. The modeled rats were treated with atorvastatin calcium and a JAK/STAT pathway inhibitor (AG490), and the levels of cardiac function-related indices, left ventricular mass index, lipid levels, serum inflammatory factors and vascular endothelial function-related indices were detected in each group. HMG-CoA reductase inhibitor improved blood pressure levels, lipid levels, serum inflammatory factor levels and cardiac function in elderly patients with essential hypertension. Both HMG-CoA reductase inhibitor and AG490 improved blood pressure levels, lipid levels, serum inflammatory factor levels and cardiac function in SHR rats. Both HMG-CoA reductase inhibitor and AG490 decreased p-JAK2/JAK2 and p-STAT3/STAT3 expression levels. Our study demonstrates that HMG-CoA reductase inhibitor improves elderly essential hypertension-induced vascular endothelial function impairment by blocking the JAK/STAT pathway.