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SOUTHERN REGIONAL MEETING ABSTRACTS Cardiovascular Club I

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SOUTHERN REGIONAL MEETING ABSTRACTS Cardiovascular Club I Abstracts SOUTHERN REGIONAL MEETING 2 ATTENUATION OF RENAL FIBROSIS AND ABSTRACTS INFLAMMATION IN NATRIURETIC PEPTIDE RECEPTOR A GENE-TARGETED MICE BY EPIGENETIC Cardiovascular Club I MECHANISMS OF SODIUM BUTYRATE- AND 11:00 AM RETINOIC ACID Thursday, February 18, 2016 P Kumar, R Periyasamy, K Pandey. Tulane University Health Sciences Center, New Orleans, LA 1 ROLE OF CYCLIN DEPENDENT KINASE INHIBITOR 10.1136/jim-2015-000035.2 P27 IN CARDIOMYOCYTE REGENERATION Purpose of Study Mice lacking functional guanylyl SK Sen, H Sadek. UT Southwestern Medical Center, Dallas, TX cyclase/natriuretic peptide receptor-A (GC-A/NPRA) gene 10.1136/jim-2015-000035.1 (Npr1) exhibit hypertension, kidney disease, and heart failure. The objective of the present study was to determine Purpose of Study Neonatal mammalian hearts have the the combined effect of sodium butyrate (NaBu), a histone ability to undergo cardiomyocyte regeneration for a short deacetylase (HDAC) inhibitor and all-trans retinoic acid period of time after birth through proliferation of pre- (ATRA) on attenuation of renal fibrosis and inflammation existing cardiomyocytes. This regenerative window is lost in Npr1 gene-disrupted mutant mice. by the first week of life coinciding with cell cycle arrest. Methods Used Adult (18–20 week old) male Npr1 gene- − The exact mechanism of how postnatal cardiomyocytes disrupted heterozygous (1-copy; Npr1+/ )wild-type regulate proliferation remains unclear. We hypothesize a (2-copy; Npr1+/+), and gene-duplicated (3-copy; Npr1++/+) Kip1 specific cyclin-dependent kinase inhibitor p27 (p27) mice were treated by injecting ATRA-NaBu hybrid drug plays a prominent role in cardiomyocyte proliferation both (1.0 mg/kg/day) intraperitoneally for 2-weeks. in the neonatal period and in adults following myocardial Summary of Results A marked attenuation in − injury. tubulo-interstitial fibrosis was observed in Npr1+/ mice after Methods Used Cardiomyocyte specific α-myosin heavy treatment with ATRA-NaBu (50%, p<0.001). Western blot chain deletion of p27 using Cre recombinase (cKO) mice analyses exhibited the reduction in renal expression of colla- were harvested and compared with wild type (WT) mice in gen type I alpha 2 and transforming growth factor-beta in − the postnatal period. Immunostaining using mitotic markers ATRA-NaBu-treated Npr1+/ mice compared with vehicle- phospho-histone 3 (pH3) and Aurora B kinase (AurB) were treated mice. A significant decrease in systolic blood pressure − used to quantify proliferation along with wheat germ agglu- was observed in ATRA-NaBu-treated Npr1+/ mice. The tinin (WGA) to determine cell size differences. ATRA-NaBu treatment enhanced plasma cGMP levels in − Cardiomyocyte and nucleation counts were done by collage- Npr1+/ , Npr1+/+,andNpr1++/+ mice. Western blot ana- nase digestion. Cardiac function was assessed using M-mode lyses confirmed the reduction in renal expression of tumor echocardiography. Conditional deletion of p27 in the adult necrosis factor-alpha and interleukin-6 in f/f − heart was also investigated using a p27 αMHC ATRA-NaBu-treated Npr1+/ mice compared with control MerCreMer mouse model (iKO) that allowed specific dele- mice. Interestingly, ATRA-NaBu significantly enhanced the tion of p27 following tamoxifen administration. These p27 levels of immunosuppressive cytokine IL-10 in the kidneys of − iKO mice were induced to explore the re-activation of cardi- Npr1+/ , Npr1+/+,andNpr1++/+ mice. Moreover, the − omyocyte mitosis as well as return of function following increased HDAC activity in Npr1+/ mice was markedly ischemic injury. reduced by ATRA-NaBu treatment compared with untreated − Summary of Results p27 cKO extended of the proliferative Npr1+/ control mice. window up to an additional week (6-fold) with no harmful Conclusions The present results provide direct evidence that effect in cardiac function. Proliferation was no longer seen by ATRA-NaBu acts as a potent antifibrotic agent and repairs the − 1 month of age. In the adult mice, p27 iKO showed renal pathology in Npr1+/ mice, which will have important re-activation of mitotic cardiomyocytes throughout the heart implications in prevention of hypertension-related renal (5-fold). In addition, we showed a decrease in cell size pathophysiological conditions. (p=0.023)withnosignificant change in heart weight/body weight ratio. Following myocardial infarction (MI), p27 iKO mice similarly showed robust proliferation throughout the 3 DIFFERENCES IN VENTRICULAR ARRHYTHMIA myocardium as well as a brisk return of cardiac function com- BURDEN BETWEEN HIGH VERSUS LOW POTENCY paredtoWTatsixweekspostMI. STATINS IN PATIENTS WITH NON-ISCHEMIC Conclusions p27 has an important role in cardiomyocyte CARDIOMYOPATHY proliferation both in extending the neonatal proliferative F Al-Saffar,1 C Bennin,2 R Kim1. 1University of Florida – Jacksonville, window and increasing the number of mitotic cardiomyocyte 2 Jacksonville, FL; Valley Cardiology, Fayettville, NC in the adult heart and may have a therapeutic role in regulat- ing cardiomyocyte cell cycle regeneration. 10.1136/jim-2015-000035.3 488 J Investig Med 2016;64:488–726 Abstracts Summary of Results The majority (63%) of the P. had metabolic syndrome (MetS). Analysis by Fisher exact test failed to show significative important correlation with risk factors like diabetes mellitus Type 2, hypertension or hyperlipidemia. 58.7% of patients had angiographic evi- dence of obstructive coronary disease (CAD). Thirty percent of patients had positive C-reactive protein. No prior myocardial infarction or strokes were found. All of them received either pharmacological or revascularization Abstract 3 Figure 1 therapy with angioplasty or bypass surgery. Conclusions In Hispanics, there is a lower incidence of Purpose of Study Ventricular arrhythmia (VA) occurs in CAD compared to Caucasians and African-Americans. We fl patients with ischemic and non-ischemic cardiomyopathy believe that persistent systemic in ammation in psoriasis in fl (NICM). Recent studies have shown that statin therapy conjunction with the up-regulation of in ammatory media- reduces the frequency of VA episodes and the number of tors associated to MetS increases the risk of developing CAD. appropriate implantable Cardioverter-Defibrillator (ICD) This shows that coronary artery disease in young P.withpsor- fl therapies in patients with NICM. We hypothesized that iasis is related to in ammation and not to others risk factors. high potency statins may be more efficacious than low This should be further investigated. potency statins in reducing the number of VA episodes. Methods Used A retrospective study of 102 patients with NICM and ICD (primary prevention) receiving statin 5 ASSOCIATIONS BETWEEN HUNTER TYPE A/B therapy between the years 2000 and 2010 at our institu- PERSONALITY TRAITS AND CARDIOVASCULAR RISK tion. Data was collected through devices for 2 years follow- FACTORS FROM CHILDHOOD TO YOUNG ing the initiation of therapy. If the study subject was ADULTHOOD already on statin, the data was collected for 2 years follow- L Bazzano, B Pollock, W Chen, E Harville. Tulane University School of Public ing ICD implantation. All registered VA episodes were indi- Health and Tropical Medicine, New Orleans, LA vidually reviewed to exclude supraventricular rhythm. Summary of Results The mean age of study subjects was 10.1136/jim-2015-000035.5 59.8 years. Eighty-nine percent were on optimal medical therapy. There was no statistical difference in the mean Purpose of Study Several studies have linked adult Type A number of VA episodes between patients taking high vs. personality with cardiovascular (CV) disease, but evidence low potency statins (p=0.333). There was no difference in is limited regarding associations between childhood person- the mean number of VA episodes between patients taking ality type and CV risk factors. Here, we use the hydrophilic versus lipophilic statins (p=0.154). Diuretics Hunter-Wolf A/B personality trait score to examine child- use was associated with significantly higher VT/VF events hood personality and its cross-sectional and longitudinal (84.4% vs. 68.3%, p= 0.024). associations with traditional CV risk factors. – Conclusions In patients with NICM with a primary pre- Methods Used From 1984 1986, 3,396 children were vention ICD and receiving statin therapy, there was a weak surveyed and multivariable linear regression was used to trend (not statistically significant) toward a fewer number test adjusted associations between personality and CV risk of VA episodes in patients receiving high (compared to factors. To test longitudinal associations, subjects were fol- low) potency statins. lowed through 2007 and general estimating equation models examined changes in risk factors and their associa- tions with childhood personality traits. 4 THE ATHEROSCLEROTIC PROCESS IN PSORIASIS IS DIRECTLY RELATED TO INFLAMMATION J Nieves,1 C Sulia,1 PI Altieri,1,2 L Figueroa,1 H Banchs,1,2 W González1. 1University of Puerto Rico, School of Medicine, San Juan, PR; 2Cardiovascular Center of Puerto Rico and the Caribbean, San Juan, PR 10.1136/jim-2015-000035.4 Purpose of Study We intended to study the morbidity and mortality in patients (P.) with psoriasis and find out if inflammation is the most important factor. Methods Used Retrospective study of 46 patients with moderate to severe psoriasis admitted to the Cardiovascular Center of Puerto Rico and the Caribbean from 2007 to 2013 due to chest pain and suspected myo- cardial infarct. Coronary angiographic reports were reviewed and analyzed statistically by Fisher exact test with risk factors like diabetes mellitus, hypertension or hyperlip- idemia. Population median age was 56 years and 72% were males. Abstract 5 Figure 1 J Investig Med 2016;64:488–726 489 Abstracts Summary of Results Mean(±SD) Hunter A/B score was 24 h: high Na diet) and PA status. LVH reduction was 96.9±11.6, with 1,730 (50.9%) Type A subjects. After indexed by left ventricular mass (LVM) and interventricular adjustment, alcohol use, gender, race, and BMI were asso- septum thickness (IVS) regression. ciated with childhood personality (p<.0001, p<.0001, Summary of Results LVM and IVS regression after treat- p=.03, and p=.06 respectively).
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