Human ApoE2 Endows Stronger Contractility in Rat Cardiomyocytes Enhancing Heart Function.
Yang WuFujie ZhaoVenkata N SureAbdulgafar IbrahimChangjiang YuSean M CarrMing-Hui ZouPublished in: Cells (2023)
(1) Background: Apolipoprotein E (ApoE) is a critical plasma apolipoprotein for lipid transport and nonlipid-related functions. Humans possess three isoforms of ApoE (2, 3, and 4). ApoE2, which exhibits beneficial effects on cardiac health, has not been adequately studied. (2) Methods: We investigated the cardiac phenotypes of the humanized ApoE knock-in (hApoE KI) rats and compared to wild-type (WT) and ApoE knock-out (ApoE KO) rats using echocardiography, ultrasound, blood pressure measurements, histology strategies, cell culture, Seahorse XF, cardiomyocyte contractility and intracellular Ca 2+ tests, and Western blotting; (3) Results: hApoE2 rats exhibited enhanced heart contractile function without signs of detrimental remodeling. Isolated adult hApoE2 cardiomyocytes had faster and stronger sarcomere contractility because of more mitochondrial energy generation and stimulation-induced fast and elevated intracellular Ca 2+ transient. The abundant energy is a result of elevated mitochondrial function via fatty acid β-oxidation. The fast and elevated Ca 2+ transient is associated with decreased sarcoplasmic reticulum (SR) Ca 2+ ATPase (SERCA2) and increased expression of cardiac ryanodine receptor 2 (RyR2) conducting a potent Ca 2+ release from SR.; (4) Conclusions: Our studies validated the association of polymorphic ApoEs with cardiac health in the rat model, and revealed the possible mechanisms of the protective effect of ApoE2 against heart diseases.
Keyphrases
- cognitive decline
- high fat diet
- left ventricular
- blood pressure
- healthcare
- mild cognitive impairment
- heart failure
- fatty acid
- public health
- smooth muscle
- atrial fibrillation
- protein kinase
- oxidative stress
- magnetic resonance imaging
- type diabetes
- computed tomography
- adipose tissue
- reactive oxygen species
- cerebral ischemia
- single cell
- squamous cell carcinoma
- binding protein
- weight loss
- skeletal muscle
- social media
- mass spectrometry
- subarachnoid hemorrhage
- south africa
- high resolution
- drug induced
- human health
- pulmonary hypertension
- ultrasound guided