Regional Heterogeneity in Gene Expression Profiles: A Transcript Analysis in Human and Rat Heart

Abstract

Background: Investigations involving biopsies of human cardiac tissue often assume that myocardial samples from a specific location are representative of the entire heart. Hypothesis: There are significant regional differences in gene expression in the heart. Methods: We used two models. In the first model, seven whole human hearts were cut in 1-cm slices from apex to base and 11 distinct regions were sampled. Full thickness left ventricular tissue was further subdivided equally into an inner, outer, and middle region. In the second model, hearts were removed from adult Sprague-Dawley rats and were divided into 4 regions. Using species-specific quantitative reverse transcriptase-polymerase chain reaction, we measured transcript levels of myosin heavy chain β (MHC-β), glucose transporter 1 (GLUT 1), and atrial natriuretic factor (ANF) in tissue samples from both models. Results: In human heart, there were significant differences in transcript levels between regions. The following patterns could be recognized among the seven hearts. ANF expression was highest in the subendocardial region. MHC-β and GLUT 1 transcript levels were higher in the right ventricle than the left ventricle. As expected, ANF transcript levels were highest in the atria, where MHC-β and GLUT 1 expression was low. Analogous to the human studies, MHC-β and GLUT 1 transcript levels were low in rat atria as compared to ventricles. In rat heart, MHC-β expression was higher in the left ventricle than the right 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 suggesting that different anatomical regions of the heart also differ in respect to gene expression.

Right-To-Left Ventricular Differences in the Expression of Mitochondrial Hexokinase and Phosphorylation of Akt

“…A higher activity of glucose metabolism is associated with a faster contraction related to myosin heavy chain (MyHC) isoform expression. Interestingly, a lower expression of MyHCβ and a higher expression of MyHCα with higher ATPase activity [56,57,58] in the RV as compared to the LV [59,60], indicate that the RV exhibits a faster muscle phenotype. Indeed, the shortening velocity of the RV muscle is greater than that of the LV [59].…”

Chronic heart failure selectively induces regional heterogeneity of insulin-responsive glucose transporters

“…Although several investigators have suggested regional differences in myocardial structure and function, potential regional differences related to glucose metabolism have been infrequently investigated (13,14,29). Because of its hydrophilic nature, glucose is unable to pass the lipid bilayer of the plasma membrane by simple diffusion, thus the rate-limiting step for cardiac glucose utilization is glucose uptake, which is preceded and induced by translocation of GLUTs from an intracellular site to the cell surface (28).…”

“…Despite the crucial role of glucose utilization in the heart and regional differences in myocardial structure and function (14,29), the potential regional pattern in the regulation of glucose transport in the healthy myocardium and during chronic HF has not been investigated. Since glucose entry across the sarcolemma is regulated by GLUT, we hypothesized that 1) insulinresponsive GLUT4 and -12 protein expression will be chamber specific in the healthy and in the failing myocardium; 2) GLUT4 and -12 protein and mRNA expression will be altered during chronic HF.…”

Activity of the Akt/GSK-3β pathway in the failing human heart before and after left ventricular assist device support

“…We have recently also shown that gene expression of markers of heart failure vary not only transmurally, but also within different regions of the left ventricle. [5] Our study and the study by Baba et al examined myocardial tissue from the apex. It is possible that even within a small anatomical region there are significant differences in protein activity.…”