Genetically determined mitochondrial preservation and cardioprotection against myocardial ischemia-reperfusion injury in a consomic rat model. Physiol Genomics 2014 Mar 01;46(5):169-76
Date
01/02/2014Pubmed ID
24380873Pubmed Central ID
PMC3949105DOI
10.1152/physiolgenomics.00118.2013Scopus ID
2-s2.0-84900798631 (requires institutional sign-in at Scopus site) 6 CitationsAbstract
Cardioprotection may be genome dependent. One example is the increased tolerance to cardiac ischemia-reperfusion (IR) in Brown Norway (BN) compared with Dahl salt-sensitive (SS) rats. By narrowing the genetic difference to chromosome 6 only, we found the consomic SS(6BN) to be similarly IR tolerant as BN. We hypothesized that better preserved mitochondrial structure and function are genetically determined and therefore critically linked to myocardial IR tolerance associated with BN chromosome 6. Langendorff-prepared BN, SS, and SS(6BN) rat hearts were subjected to IR, while corresponding controls were continuously perfused. Though largely equal in nonischemic controls, assessment of functional data and ventricular infarct size in IR experiments confirmed that BN and SS(6BN) have an equally higher tolerance to IR than SS hearts. This was complemented by equally better preserved mitochondrial structure, oxidative phosphorylation, and calcium retention capacity in BN and SS(6BN) vs. SS hearts. For the first time, our data indicate that SS(6BN) are as resistant to IR injury as BN hearts in mitochondrial and myocardial function and viability compared with SS hearts. These findings not only link myocardial and mitochondrial protection in a genetic model but also suggest that genetic information on rat chromosome 6 is critical for mitochondrial preservation and IR tolerance.
Author List
Nabbi R, Gadicherla AK, Kersten JR, Stowe DF, Lazar J, Riess MLAuthor
Ashish K. Gadicherla PhD Assistant Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsCalcium
Disease Models, Animal
Heart
Male
Mitochondria, Heart
Myocardial Infarction
Myocardial Reperfusion Injury
Oxidative Phosphorylation
Rats
Rats, Inbred BN
Rats, Inbred Dahl
