The effect of cardiac ischemic preconditioning on rat left ventricular gene expression profile

Abstract

Ischemic preconditioning (IPC) is a phenomenon where heart is rendered more resistant to subsequent ischemia-reperfusion (I-R)-induced injury by one or more brief episodes of I-R. The mechanisms responsible for cardio-protective effects of IPC are not well characterized. The objective of the study was to characterize gene expression profiles in the left ventricle of male Wistar rat hearts exposed to I-R or IPC followed by I-R. Group 1 included hearts that were only perfused for 30 min. Group 2 included hearts that underwent 30 min perfusion followed by 40 min I and 30 min R. Group 3 comprised 30 min perfused hearts that were subjected to IPC (5 min I + 10 min R + 5 min I + 10 min R) followed by I-R. Total RNAs were isolated from left ventricular tissues. Codelink gene expression system (GE Healthcare) was used for cRNA target preparation, hybridization of microarrays (Rat UniSet 10 K CodeLink bioarrays, GE Healthcare) and detection. Microarrays were scanned with Affymetrix 428 Array scanner. Data analyses were carried out with GeneSifter microarray data analysis software. We determined a total of 140 transcripts (> or =2-fold change) whose expressions were changed (44 up-regulated and 96 down-regulated) accompanying to I-R injury compared to perfused only hearts. Twenty-three transcripts including Ryr3, Crk, Dio1, Npy1r, Ptpra, Cyp51 that were down-regulated by I-R injury, were up-regulated by cardiac IPC. IPC down-regulated the expression of several transcripts including Atf3 (activating transcription factor 3), carboxypeptidase A1 (Cpa1), Slc38a4, Blk which were up-regulated by I-R. In conclusion, evaluation of global gene expression profiling via microarray-based technologies provides a molecular portrait of cardiac IPC of the left ventricular tissue of rat heart.

Identification of potential target genes of cardioprotection against ischemia–reperfusion injury by express sequence tags analysis in rat hearts

“…In spite of the identification of these signaling pathways, the precise mechanism by which these pathways reduce cell death is only beginning to be understood [10]. Recently, genetic profiling of heart and heart disease models was performed to develop strategies for enhancing beneficial gene expression changes, and inhibiting potentially harmful ones, during cardiac development [11], atrial fibrillation [12], oxidative stress-induced cardiac myocyte apoptosis [13], and ischemic preconditions [14]. Furthermore, large-scale, specific, disease-targeted gene expression profiling analyses have provided a large amount of information as like a whole cDNA library with expressed sequence tags (ESTs) in heart and its specific state [15,16].…”

Preconditioning boosts regenerative programmes in the adult zebrafish heart

“…In the mammalian heart, short bouts of non-lethal cardiac or non-cardiac insults elicit cytoprotection against subsequent prolonged ischaemia and reperfusion [ 7 ]. The preconditioned phenotype is characterized by the elevated expression of pro-angiogenic, antioxidant and cardioprotective genes [ 17 , 19 , 40 ]. A mechanistic rationale for new drug therapies that mimic these powerful protective responses remains unfortunately still unclear.…”

Tumor Necrosis Factor Alpha and Insulin-Like Growth Factor 1 Induced Modifications of the Gene Expression Kinetics of Differentiating Skeletal Muscle Cells

“…Importantly, we identified genes inversely regulated during skeletal myocyte differentiation compared with differentiation under TNF-α stimulus, but have not yet been described in the context of skeletal muscle or TNF-α effect on muscle cells. Some differentiation and TNF-α-regulated genes have been described in smooth or heart muscle, or muscle progenitor cells, but not in skeletal muscle, including Cpa1 [ 110 ], Parm1 [ 111 ], and Serpinb2 [ 112 ] ( Fig 5 ). Parm1 expression was detected in the muscle progenitor cells of the somites [ 111 ].…”