Analysis of region specific gene expression patterns in the heart and systemic responses after experimental myocardial ischemia

Abstract

AimsIschemic myocardial injury leads to the activation of inflammatory mechanisms and results in ventricular remodeling. Although great efforts have been made to unravel the molecular and cellular processes taking place in the ischemic myocardium, little is known about the effects on the surrounding tissue and other organs. The aim of this study was to determine region specific differences in the myocardium and in distant organs after experimental myocardial infarction by using a bioinformatics approach.Methods and ResultsA porcine closed chest reperfused acute myocardial infarction model and mRNA microarrays have been used to evaluate gene expression changes. Myocardial infarction changed the expression of 8903 genes in myocardial-, 856 in hepatic- and 338 in splenic tissue. Identification of myocardial region specific differences as well as expression profiling of distant organs revealed clear gene-regulation patterns within the first 24 hours after ischemia. Transcription factor binding site analysis suggested a strong role for Kruppel like factor 4 (Klf4) in the regulation of gene expression following myocardial infarction, and was therefore investigated further by immunohistochemistry. Strong nuclear Klf4 expression with clear region specific differences was detectable in porcine and human heart samples after myocardial infarction.ConclusionApart from presenting a post myocardial infarction gene expression database and specific response pathways, the key message of this work is that myocardial ischemia does not end at the injured myocardium. The present results have enlarged the spectrum of organs affected, and suggest that a variety of organ systems are involved in the co-ordination of the organism´s response to myocardial infarction.

Identification of Malonylation, Succinylation, and Glutarylation in Serum Proteins of Acute Myocardial Infarction Patients

“…Our results showed the level of malonylation, succinylation, and glutarylation of serum proteins was reduced in acute myocardial infarction, but SIRT5 level was unchanged after acute myocardial infarction. As there are reports that SIRT5 is abundant and actively modifies malonylation, succinylation, and glutarylation in liver, and liver metabolism could be modified during acute myocardial infarction, it is possible that the reduction of serum protein malonylation, succinylation, and glutarylation happens in liver.…”

The Arginase Pathway in Neonatal Brain Hypoxia-Ischemia

“…ARG is upregulated during ischemia-reperfusion and whether this is protective or detrimental is organ-dependent. ARG-1 is one of the most abundant and fastest upregulated genes [6,84] with increased activity [85–87] following ischemia-reperfusion injury in models of myocardial infarction. This upregulation has been shown to be largely detrimental, mostly likely via decreasing NO levels [87] and bioavailability [88].…”

Spatiotemporal single-cell analysis reveals critical roles of mechano-sensing genes at the border zone in remodeling after myocardial infarction

“…However, the cellular and molecular mechanisms underlying remodeling processes in the BZ remain unclear. Previous studies examined expressions of RNA or proteins using myocardial tissues around the BZ dissected from infarcted hearts and reported that expressions of genes associated with angiogenesis, in ammation, apoptotic response and B-type natriuretic peptide (BNP) were highly up-regulated in the BZ 11,[19][20][21] . However, it was di cult to precisely de ne spatiotemporal molecular behaviors after MI at the single-cell level due to the ambiguous spatial localization of the BZ and the analysis using bulk tissues.…”