Renal sympathetic denervation attenuates left ventricle hypertrophy in spontaneously hypertensive rats by suppressing the Raf/MEK/ERK signaling pathway.

OBJECTIVE: To explore the effect of renal sympathetic denervation (RSD) on left ventricle hypertrophy and the Raf/MEK/ERK signaling pathway in spontaneously hypertensive rats (SHRs). METHODS: SHRs were divided into SHR, SHR + Sham, SHR + RSD and SHR + U0126 groups, with WKY rats as the baseline controls. The blood pressure of rats was observed, while myocardial fibrosis was evaluated through Masson staining. Thereafter, real-time quantitative polymerase chain reaction (qRT-PCR) was carried out to determine the levels of myocardial-hypertrophy-related markers, and Western blotting was used to measure the activity of the Raf/MEK/ERK signaling pathway. RESULTS: In comparison with the WKY group, significant increases were observed in the systolic pressure and diastolic pressure of rats from the other four groups at different time points after surgery. In addition, rats in these groups had obvious increases in LVMI, renal NE and IVSd and decreases in LVEDd, LVEF and LVFS. In addition, the CVF of myocardial tissues was increased, with the upregulation of ANP, BNP and ß-MHC and the downregulation of α-MHC. For the activity of the Raf/MEK/ERK signaling pathway, the levels of p-Raf/Raf, p-MEK/MEK and p-ERK1/2/ERK1/2 were all remarkably elevated (all P < .05). Further comparison with the SHR group showed that the above indexes in the rats were significantly improved in the RSD group and SHR + U0126 group (all P < .05). CONCLUSION: RSD may decrease blood pressure, mitigate hypertension-induced left ventricle hypertrophy and improve cardiac function efficiently in SHRs via the suppression of the Raf/MEK/ERK signaling pathway.

Trimetazidine Effect on the Cardiac Autonomic Nerve System after Percutaneous Coronary Intervention in Coronary Heart Disease: A Propensity-score Matched Study.

OBJECTIVE: To assess the effects of trimetazidine (TMZ) added to conventional drug therapy on cardiac autonomic nervous CANS in patients with coronary heart disease (CHD) after the percutaneous coronary intervention (PCI). STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY:  Department of Cardiology, The Second Hospital of Hebei Medical University, Hebei, China, from May 2018 to September 2019. METHODOLOGY: The study included 50 patients with CHD after a successful PCI who received trimetazidine plus conventional therapy were included as cases (exposed group), and 50 matched patients were identified as controls (non-exposed group). Heart rate (HR) and heart rate variability (HRV) parameters including sympathetic activity (SDNN, LF), parasympathetic activity (RMSSD, pNN50, SDSD, HF), and sympathovagal balance (LF/HF ratio) were used to evaluate CANS function. RESULTS: There were no statistical differences in the HR and HRV parameters before and after PCI (p>0.05). In the non-exposed group, conventional therapy significantly improved the HRV parameters (all p<0.05), while not affecting HR (p>0.05). In the exposed group, all HRV parameters except HR were improved after 4 weeks of treatment. After 4 weeks of treatment, the exposed group had higher parasympathetic-nerve activity, lower sympathetic-nerve activity, and LF/HF ratio compared to the non-exposed group (all p<0.05). CONCLUSIONS: The application of TMZ based on conventional therapy effectively improved the CANS in CHD patients who underwent PCI. KEY WORDS: Coronary heart disease, Percutaneous coronary intervention, Trimetazidine, Cardiac autonomic nervous system, Heart rate variability.

Two Novel Mutations (G774A and A1685G) Causing Coagulation Factor XII Deficiency in a Patient with Acute Inferior Myocardial Infarction.

OBJECTIVE: To identify the gene mutation of the coagulation factor XII (FXII) in a patient with FXII deficiency and acute inferior myocardial infarction. METHODS: The proband was a 51-year-old Chinese man who was diagnosed with acute inferior myocardial infarction and had a history of FXII deficiency. The patient presented with a prolonged activated partial thromboplastin time (160 s) and decreased FXII activity (2.3%) and FXII antigen (1%). DNA sequence analysis of the FXII gene was performed by next generation sequencing. The mutant FXII cDNAs were constructed in an expression plasmid vector and transfected into 293T cells. The expression of FXII antigen was detected by western blot. RESULTS: Sequencing of the FXII gene revealed two novel heterozygous mutations, one at exon 8 (G774A; p: W258X) and the other at exon 14 (A1685G; p: D562G). Western blot showed that the FXII antigens were detected only in the supernatant and whole cell lysate of the wild-type and A1685G mutant type, but not in G774A or G774A plus the A1685G mutant type. In addition, the results showed that secretion but not synthesis of A1685G mutant protein was markedly reduced compared to the wild type. CONCLUSION: The present study indicated that the G774A mutation might impair the secretion and synthesis of FXII protein, while the A1685G mutation only influences the secretion of FXII protein. The definition of these new mutations could be useful tools for analyzing the intracellular protein transport and structure-function relationship of FXII protein transport in the future.