Regional Differences of Gene Expression in Human and Rodent Heart

Abstract

Background: Investigations involving human cardiac tissue have rarely considered the anatomical site from which tissue or biopsy samples originate. It is often assumed that myocardial samples from a specific location represent the entire heart. However, animal studies suggest regional differences in gene and protein expression. Hypothesis: There are significant regional differences in gene expression in the human heart. Methods: We used two models to study this hypothesis. In the first, seven whole human hearts were obtained from patients who had donated hearts for scientific research. Table 1 shows the characteristics of the seven patients. The hearts were cut in 1 cm slices from apex to base. Samples from the apex, anterior wall, lateral wall, posterior wall, septum, and papillary muscle were obtained from both left and right ventricle. Tissue was also obtained from left and right atrium. Full thickness left ventricular tissue was further subdivided equally into inner, outer, and middle region. In the second model, hearts were removed from 300–350 g Sprague-Dawley rats and were divided into atria, right ventricle, left ventricle apex and base. Using quantitative RT-PCR, we measured transcript levels of MHC-beta, GLUT 1, and ANF in tissue samples from both models. Results: In human samples, there were significant differences in transcript levels between regions; however, only a few distinguishable patterns could be recognized among the seven hearts. ANF expression was highest in the inner one third of the myocardium. MHC beta and GLUT 1 transcript levels were increased in the right ventricle compared to left ventricle. In the atria, ANF transcript levels were highly expressed, while MHC beta and GLUT 1 expression was low. Furthermore, MHC beta expression was higher in right atria compared to left atria. Analogous to the human studies, MHC beta and GLUT 1 transcript levels were low in rat atria as compared to ventricles. On the other hand, MHC beta expression was higher in the left ventricle while GLUT 1 expression was not significantly different between ventricles. Conclusion: Despite the large variability in transcript levels among different regions in human hearts, certain patterns in gene expression emerged. These included differences between right and left ventricle, right and left atria, atria and ventricle, and between inner and outer regions of the myocardium. Different anatomical regions of the heart also differ in respect to gene expression. Tabled 1Patient characteristicsAge35356671658716SexMMFFMMFRaceCCCCCCCCause of deathSepsisCrush InjuryBrain CancerMIMIStrokeSuicideComorbid diseaseHTN, CRIHTN, obesityHTN, IDDMHTN, hypothyroidGross pathologyNormalNormalNormalHypertrophyDilatedHypertophyNormalC = caucasian, HTN = hypertension, CRI = chronic renal insufficiency, IDDM = insulin dependent diabetes, MI = myocardial infarction Open table in a new tab C = caucasian, HTN = hypertension, CRI = chronic renal insufficiency, IDDM = insulin dependent diabetes, MI = myocardial infarction