Effect of Renal Denervation on Suppression of PVC and QT Prolongation in a Porcine Model of Acute Myocardial Infarction

BACKGROUND AND OBJECTIVES: Antiarrhythmic effect of renal denervation (RDN) after acute myocardial infarction (AMI) remains unclear. The goal of this study was to evaluate the effect of RDN on ventricular arrhythmia (VA) after AMI in a porcine model.METHODS: Twenty pigs were randomly divided into 2 groups based on RDN (RDN, n=10; Sham, n=10). After implanting a loop recorder, AMI was induced by occlusion of the middle left anterior descending coronary artery. Catheter-based RDN was performed for each renal artery immediately after creating AMI. Sham procedure used the same method, but a radiofrequency current was not delivered. Electrocardiography was monitored for 1 hour to observe VA. One week later, the animals were euthanized and the loop recorder data were analyzed.RESULTS: Ventricular fibrillation event rate and the interval from AMI creation to first VA in acute phase were not different between the 2 groups. However, the incidence of premature ventricular complex (PVC) was lower in the RDN than in the Sham. Additionally, RDN inhibited prolongation of the corrected QT (QTc) interval after AMI. The frequency of non-sustained or sustained ventricular tachycardia, arrhythmic death was lower in the RDN group in the early period.CONCLUSIONS: RDN reduced the incidence of PVC, inhibited prolongation of the QTc interval, and reduced VA in the early period following an AMI. These results suggest that RDN might be a therapeutic option in patients with electrical instability after AMI.

Effect of Renal Denervation on Suppression of PVC and QT Prolongation in a Porcine Model of Acute Myocardial Infarction

BACKGROUND AND OBJECTIVES@#Antiarrhythmic effect of renal denervation (RDN) after acute myocardial infarction (AMI) remains unclear. The goal of this study was to evaluate the effect of RDN on ventricular arrhythmia (VA) after AMI in a porcine model.@*METHODS@#Twenty pigs were randomly divided into 2 groups based on RDN (RDN, n=10; Sham, n=10). After implanting a loop recorder, AMI was induced by occlusion of the middle left anterior descending coronary artery. Catheter-based RDN was performed for each renal artery immediately after creating AMI. Sham procedure used the same method, but a radiofrequency current was not delivered. Electrocardiography was monitored for 1 hour to observe VA. One week later, the animals were euthanized and the loop recorder data were analyzed.@*RESULTS@#Ventricular fibrillation event rate and the interval from AMI creation to first VA in acute phase were not different between the 2 groups. However, the incidence of premature ventricular complex (PVC) was lower in the RDN than in the Sham. Additionally, RDN inhibited prolongation of the corrected QT (QTc) interval after AMI. The frequency of non-sustained or sustained ventricular tachycardia, arrhythmic death was lower in the RDN group in the early period.@*CONCLUSIONS@#RDN reduced the incidence of PVC, inhibited prolongation of the QTc interval, and reduced VA in the early period following an AMI. These results suggest that RDN might be a therapeutic option in patients with electrical instability after AMI.

Expression of Class I and Class II a/b Histone Deacetylase is Dysregulated in Hypertensive Animal Models

BACKGROUND AND OBJECTIVES: Dysregulation of histone deacetylase expression and enzymatic activity is associated with a number of diseases. It has been reported that protein levels of histone deacetylase (HDAC)1 and HDAC5 increase during human pulmonary hypertension, and that the enzymatic activity of HDAC6 is induced in a chronic hypertensive animal model. This study investigated the protein expression profiles of class I and II a/b HDACs in three systemic hypertension models. SUBJECTS AND METHODS: We used three different hypertensive animal models: (i) Wistar-Kyoto rats (n=8) and spontaneously hypertensive rats (SHR; n=8), (ii) mice infused with saline or angiotensin II to induce hypertension, via osmotic mini-pump for 2 weeks, and (iii) mice that were allowed to drink L-N(G)-nitro-L-arginine methyl ester (L-NAME) to induce hypertension. RESULTS: SHR showed high systolic, diastolic, and mean blood pressures. Similar increases in systolic blood pressure were observed in angiotensin II or L-NAME-induced hypertensive mice. In SHR, class IIa HDAC (HDAC4, 5, and 7) and class IIb HDAC (HDAC6 and 10) protein expression were significantly increased. In addition, a HDAC3 protein expression was induced in SHR. However, in L-NAME mice, class IIa HDAC protein levels (HDAC4, 5, 7, and 9) were significantly reduced. HDAC8 protein levels were significantly reduced both in angiotensin II mice and in SHR. CONCLUSION: These results indicate that dysregulation of class I and class II HDAC protein is closely associated with chronic hypertension.

miR-18a-5p MicroRNA Increases Vascular Smooth Muscle Cell Differentiation by Downregulating Syndecan4

BACKGROUND AND OBJECTIVES: Differentiation and de-differentiation of vascular smooth muscle cells (VSMCs) are important events in atherosclerosis and restenosis after angioplasty. MicroRNAs are considered a key regulator in cellular processes such as differentiation, proliferation, and apoptosis. Here, we report the role of new miR-18a-5p microRNA and its downstream target genes in VSMCs and in a carotid balloon injury model. MATERIALS AND METHODS: Expression of miR-18a-5p and its candidate genes was examined in VSMCs and in a carotid artery injury model by quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and microRNA microarray analysis. VSMC differentiation marker genes including smooth muscle (SM) alpha-actin and SM22alpha were determined by Western blot, qRT-PCR, and a SM22alpha promoter study. Gene overexpression or knockdown was performed in VSMCs. RESULTS: miR-18a-5p was upregulated in the rat carotid artery at the early time after balloon injury. Transfection of the miR-18a-5p mimic promoted the VSMC differentiation markers SM alpha-actin and SM22alpha. In addition, miR-18a-5p expression was induced in differentiated VSMCs, whereas it decreased in de-differentiated VSMCs. We identified syndecan4 as a downstream target of miR-18-5p in VSMCs. Overexpression of syndecan4 decreased Smad2 expression, whereas knockdown of syndecan4 increased Smad2 expression in VSMCs. Finally, we showed that Smad2 induced the expression of VSMC differentiation marker genes in VSMCs. CONCLUSION: These results indicate that miR-18a-5p is involved in VSMC differentiation by targeting syndecan4.

Clinical Characteristics of Autosomal Dominant Giant Platelet Syndromes and Mutation Analysis of MYH9 / 대한혈액학회지

BACKGROUND: The autosomal dominant giant platelet syndromes (GPS), characterized by triads of giant platelets, thrombocytopenia, and Dohle-like leukocyte inclusions are caused by MYH9 mutation, a gene encoding the nonmuscle myosin heavy chain-IIA. This study was aimed to identify the Korean GPS patients and to define clinical findings and molecular characteristics on them. METHODS: After taking a family history, platelets were counted using hematologic autoanalyzer and peripheral blood smear (PBS) was examined for platelet size and number, and the presence of leukocyte inclusions. Mutation of MYH9 was studied from mononuclear cells from PB by direct sequencing of previously known 8 exons after PCR amplification of genomic DNA. RESULTS: Twenty patients from 5 unrelated families were diagnosed as GPS. Giant platelets, greater than red cells on PBS, were found to be 3.1% of platelet (range, 1~11%). The median platelet count was 61,000/microliter. Inclusion bodies were found in 3 families. Two families had previously reported mutations. Family I had Arg1944Ter in exon 40, located in the tail portion of myosin, while Family IV had Lys373Asn in exon 10, located in the proximal portion of myosin head. The mutations were found only in affected patients, but not in normal siblings or unrelated families. CONCLUSION: In this study, we identified several families with autosomal dominant GPS. Two families had known MYH9 mutations, Arg1944Ter and Lys373Asn. The search for unknown mutations in the remaining families as well as study of protein structural and functional alteration seems to be necessary for further delineation of these rare genetic disorders.