Comparative Analysis of mRNA Isoform Expression in Cardiac Hypertrophy and Development Reveals Multiple Post-Transcriptional Regulatory Modules

Cardiac hypertrophy is enlargement of the heart in response to physiological or pathological stimuli, chiefly involving growth of myocytes in size rather than in number. Previous studies have shown that the expression pattern of a group of genes in hypertrophied heart induced by pressure overload resembles that at the embryonic stage of heart development, a phenomenon known as activation of the “fetal gene program”. Here, using a genome-wide approach we systematically defined genes and pathways regulated in short- and long-term cardiac hypertrophy conditions using mice with transverse aortic constriction (TAC), and compared them with those regulated at different stages of embryonic and postnatal development. In addition, exon-level analysis revealed widespread mRNA isoform changes during cardiac hypertrophy resulting from alternative usage of terminal or internal exons, some of which are also developmentally regulated and may be attributable to decreased expression of Fox-1 protein in cardiac hypertrophy. Genes with functions in certain pathways, such as cell adhesion and cell morphology, are more likely to be regulated by alternative splicing. Moreover, we found 3′UTRs of mRNAs were generally shortened through alternative cleavage and polyadenylation in hypertrophy, and microRNA target genes were generally de-repressed, suggesting coordinated mechanisms to increase mRNA stability and protein production during hypertrophy. Taken together, our results comprehensively delineated gene and mRNA isoform regulation events in cardiac hypertrophy and revealed their relations to those in development, and suggested that modulation of mRNA isoform expression plays an importance role in heart remodeling under pressure overload

The longitudinal outcome of canine (K9) myxomatous mitral valve disease (LOOK-Mitral) registry: Baseline treatment characteristics

Objectives: To describe the medical treatment prescribed or modified by veterinary cardiologists at the enrollment visit in dogs included in the longitudinal outcome of canine (K9) myxomatous mitral valve disease (MMVD) registry (LOOK-mitral registry) and to evaluate the influence of the EPIC trial and other selected variables on cardiologist prescription habits. Animals: The medical records of 6,102 dogs enrolled in the LOOK_mitral registry between 2015 and 2018 were retrospectively reviewed and 6,016 dogs were included. Results: A medical treatment was prescribed by a cardiologist to 2,599 dogs (15% Stage-B1, 90% Stage-B2 and to all dogs in Stage-C). Angiotensin converting enzyme inhibitors (Ace-i) were the treatment most commonly prescribed for dogs in Stage-B1 (n = 352, 9%). The combination of pimobendan and an Ace-i was the most common treatment in Stage-B2 dogs (n = 367, 41%). Furosemide, an Ace-i, and pimobendan was the most common cardiac medical treatment prescribed for ACVIM Stage-C dogs (n = 704, 57%). Within each stage, dogs with larger left atrial and left ventricular dimensions were more likely to receive Ace-i, pimobendan or spironolactone. There was a four-fold increase in pimobendan prescription in Stage-B2 dogs after the publication of the EPIC trial. Moreover, a 15% reduction in Ace-i prescription and a 30% reduction in spironolactone prescription occurred after EPIC. In 974 dogs, a medical treatment was prescribed by the referring veterinarian. This was not changed (12%), modified (74%), or discontinued (14%) by the cardiologist. Conclusions: The EPIC trial and the echocardiographic assessment of left atrial and ventricular dimensions influence cardiologists’ prescription habits

Predictors of reoccurrence of congestive signs within 180 days after successful treatment of the first episode of congestive heart failure in dogs with myxomatous mitral valve disease

Introduction: Myxomatous mitral valve disease (MMVD) is the most common cause of left-sided congestive heart failure in dogs. We sought to identify predictors of first reoccurrence of congestive signs (CS) within 180 days in dogs with MMVD and clinically stable heart failure. Animals: A total of 445 dogs affected by stable American College of Veterinary Internal Medicine (ACVIM)–Stage-C MMVD were included, 106 in the reoccurrence group (RG) and 339 in no reoccurrence group (NRG). Patients were considered “stable” if medical treatment had been unchanged for at least 4 weeks since the first identification of CS. Methods: Medical records of dogs with stable ACVIM–Stage-C MMVD included in a registry of dogs affected by MMVD were reviewed. Follow-up was required for inclusion in this investigation. Logistic regression was used to identify clinical and echocardiographic variables that independently predict first reoccurrence of CS. Results: Baseline left atrial-aortic ratio (p=0.022, OR: 1.89, 90% CI: 1.20–2.98), left ventricular internal diameter at end-diastole (LVIDd_N) (p=0.014, OR: 2.84, 90% CI: 1.41–5.77), peak velocity of early diastolic transmitral flow (p=0.049, OR: 1.81, 90% CI: 1.10–3.00) and furosemide daily dosage (p=0.039, OR: 1.19, 90% CI: 1.04–1.37) were associated with reoccurrence of CS in univariable analyses. The LVIDd_N (p=0.014) remained significant in the multivariable analysis, but the area under the receiver operator characteristic curve was 0.57. Conclusion: This study failed to identify accurate predictors of reoccurrence of CS. However, dogs with larger value of LVIDd_N are more likely to have reoccurrence of CS within 180 days

The Longitudinal Outcome Of Canine (K9) myxomatous mitral valve disease (LOOK-Mitral registry): Baseline characteristics

Introduction: The Longitudinal Outcome Of Canine (K9) myxomatous mitral valve disease (MMVD) registry (LOOK-Mitral registry) was established to describe the natural history and predictors of outcome in dogs affected by MMVD. This study was intended to describe the baseline characteristics of dogs in the LOOK-mitral registry. Animals: Dogs with echocardiographic evidence of MMVD were prospectively enrolled by thirteen referral centers. Results: A total of 6102 dogs with MMVD were included. The median age was 10 years (1–19 years), and mixed breed was the most common breed (n = 1,360, 22%). Concomitant diseases were reported in 2459 dogs with chronic respiratory diseases occurring most frequently (14%), followed by the presence of azotemia (6%) and orthopedic diseases (5%). Regarding disease severity, 65% of dogs were in ACVIM Stage-B1, 15% in Stage-B2, and 20% in Stage-C. Dogs in Stage-B1 were younger (p<0.001) than dogs in other stages. Murmur intensity, heart rate during physical examination, and radiographic vertebral heart score were positively associated with the stage. Dogs in Stage-C were more likely to have tachypnea (p<0.001), dyspnea (p<0.001), cough (p<0.001), syncopal episodes (p<0.001), and tachyarrhythmias (p<0.001) compared to dogs in Stage-B1 and B2. Echocardiographic indices of left atrial and ventricular size were positively correlated with the ACVIM stage. Interestingly, 4% of dogs that weighed <20 kg had an increased normalized end-systolic left ventricle internal diameter (>1.26). Conclusions: This study contributes to a better understanding of the clinical characteristics of dogs affected by MMVD and provides new findings that may be of clinical relevance

First-Year College Students’ Time Use

How students manage their time is critical for academic performance and is an important component of self-regulated learning. The purpose of the present study was to examine relationships among first-year college students’ (N = 589) time use, academic self-regulation, and target and actual grade point average (GPA) at three time points. Findings showed that students planned and spent less time on academics than socializing and work obligations in their first semester. Students generally planned to spend more time on academics in the second semester. Academic time use (planned and actual academic hours) related to higher self-regulated learning and target GPA in the first and second semester. Students who were farther away from their first-semester target lowered their second-semester target GPA instead of planning more time in academics. Students exceeding their target first-semester GPA planned to socialize more in the second semester. Orientation and transition programs that assist students may need to revisit time management and planning midway through the year to address potentially inadequate self-regulated learning in the first year of college. © The Author(s) 2016