Selective enhancement of cardiomyocyte efficiency results in a pernicious heart condition.
Jody GroenendykQian WangCory WaggDukgyu LeeAlison RobinsonAmy BarrPeter E LightGary D LopaschukLuis B AgellonMarek MichalakPublished in: PloS one (2020)
Transgenic mice with selective induction of calreticulin transgene expression in cardiomyocytes (CardiacCRT+) were analyzed. CardiacCRT+ cardiomyocytes showed increased contractility and Ca2+ transients. Yet, in vivo assessment of cardiac performance, and ischemic tolerance of CardiacCRT+ mice demonstrated right ventricle dilation and reduced cardiac output, increased QT interval and decreased P amplitude. Paradoxically, ex vivo working hearts from CardiacCRT+ mice showed enhanced ischemic cardio-protection and cardiac efficiency. Under aerobic conditions, CardiacCRT+ hearts showed less efficient cardiac function than sham control hearts due to an increased ATP production from glycolysis relative to glucose oxidation. During reperfusion, this inefficiency was reversed, with CardiacCRT+ hearts exhibiting better functional recovery and increased cardiac efficiency compared to sham control hearts. On the other hand, mechanical stretching of isolated cardiac fibroblasts activated the IRE1α branch of the unfolded protein response pathway as well as induction of Col1A2 and TGFβ gene expression ex vivo, which were all suppressed by tauroursodeoxycholic acid.
Keyphrases
- left ventricular
- gene expression
- heart failure
- type diabetes
- cerebral ischemia
- high fat diet induced
- acute myocardial infarction
- atrial fibrillation
- endoplasmic reticulum stress
- transforming growth factor
- nitric oxide
- hydrogen peroxide
- mitral valve
- high glucose
- skeletal muscle
- binding protein
- blood glucose
- insulin resistance
- resting state
- subarachnoid hemorrhage
- smooth muscle
- double blind
- pulmonary artery