Perturbations in myocardial perfusion and oxygen balance in swine with multiple risk factors: a novel model of ischemia and no obstructive coronary artery disease

Wouw, Jens van de; Sorop, Oana; Drie, Ruben W. A. van; Duin, Richard van; Nguyen, Isabel T.N.; Joles, Jaap A.; Verhaar, Marianne C.; Merkus, Daphne; Duncker, Dirk J.

doi:10.1007/s00395-020-0778-2

Cited by 36 publications

(45 citation statements)

References 67 publications

(122 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Inflammation, especially interleukin-6 overproduction in smooth vascular cells, is an important contributor to atherogenesis. Interestingly, interleukin-6 production has been reported to result from impaired Parkin-induced mitophagy (Tyrrell et al, 2020). These findings all indicate that the inactivation of mitophagy is associated with various kinds of myocardial stress, while the improvement of mitophagy enhances myocardial function (De et al, 2020;Lamprou et al, 2020;Takov et al, 2020).…”

Section: The Dual Role Of Mitophagy In Myocardial Damage the Cardioprotective Effects Of Mitophagymentioning

confidence: 93%

RETRACTED: Molecular Perspectives of Mitophagy in Myocardial Stress: Pathophysiology and Therapeutic Targets

Kimberlee

et al. 2021

Front. Physiol.

View full text Add to dashboard Cite

A variety of complex risk factors and pathological mechanisms contribute to myocardial stress, which ultimately promotes the development of cardiovascular diseases, including acute cardiac insufficiency, myocardial ischemia, myocardial infarction, high-glycemic myocardial injury, and acute alcoholic cardiotoxicity. Myocardial stress is characterized by abnormal metabolism, excessive reactive oxygen species production, an insufficient energy supply, endoplasmic reticulum stress, mitochondrial damage, and apoptosis. Mitochondria, the main organelles contributing to the energy supply of cardiomyocytes, are key determinants of cell survival and death. Mitophagy is important for cardiomyocyte function and metabolism because it removes damaged and aged mitochondria in a timely manner, thereby maintaining the proper number of normal mitochondria. In this review, we first introduce the general characteristics and regulatory mechanisms of mitophagy. We then describe the three classic mitophagy regulatory pathways and their involvement in myocardial stress. Finally, we discuss the two completely opposite effects of mitophagy on the fate of cardiomyocytes. Our summary of the molecular pathways underlying mitophagy in myocardial stress may provide therapeutic targets for myocardial protection interventions.

show abstract

Section: The Dual Role Of Mitophagy In Myocardial Damage the Cardioprotective Effects Of Mitophagymentioning

confidence: 93%

RETRACTED: Molecular Perspectives of Mitophagy in Myocardial Stress: Pathophysiology and Therapeutic Targets

Kimberlee

et al. 2021

Front. Physiol.

View full text Add to dashboard Cite

show abstract

“…Small interfering RNAs (siRNAs) for FUNDC1 and Atf6 and the negative control (Mission, Sigma-Aldrich Corp., St Louis, MO) were used according to the manufacturer's instructions [ 44 , 45 ]. Following isolation, cardiomyocytes were cultured for 48 h prior to transfection with siRNAs at a concentration of 50 nM using Lipofectamine® RNAiMAX (Invitrogen, Carlsbad, CA) [ 46 , 47 ]. Following 6 h of incubation in Optimem®, the medium was removed and replaced with 5% FBS in DMEM/M199.…”

Section: Methodsmentioning

confidence: 99%

Mitophagy coordinates the mitochondrial unfolded protein response to attenuate inflammation-mediated myocardial injury

et al. 2021

View full text Add to dashboard Cite

Mitochondrial dysfunction is a fundamental challenge in septic cardiomyopathy. Mitophagy and the mitochondrial unfolded protein response (UPR mt ) are the predominant stress-responsive and protective mechanisms involved in repairing damaged mitochondria. Although mitochondrial homeostasis requires the coordinated actions of mitophagy and UPR mt , their molecular basis and interactive actions are poorly understood in sepsis-induced myocardial injury. Our investigations showed that lipopolysaccharide (LPS)-induced sepsis contributed to cardiac dysfunction and mitochondrial damage. Although both mitophagy and UPR mt were slightly activated by LPS in cardiomyocytes, their endogenous activation failed to prevent sepsis-mediated myocardial injury. However, administration of urolithin A, an inducer of mitophagy, obviously reduced sepsis-mediated cardiac depression by normalizing mitochondrial function. Interestingly, this beneficial action was undetectable in cardiomyocyte-specific FUNDC1 knockout (FUNDC1 CKO ) mice. Notably, supplementation with a mitophagy inducer had no impact on UPR mt , whereas genetic ablation of FUNDC1 significantly upregulated the expression of genes related to UPR mt in LPS-treated hearts. In contrast, enhancement of endogenous UPR mt through oligomycin administration reduced sepsis-mediated mitochondrial injury and myocardial dysfunction; this cardioprotective effect was imperceptible in FUNDC1 CKO mice. Lastly, once UPR mt was inhibited, mitophagy-mediated protection of mitochondria and cardiomyocytes was partly blunted. Taken together, it is plausible that endogenous UPR mt and mitophagy are slightly activated by myocardial stress and they work together to sustain mitochondrial performance and cardiac function. Endogenous UPR mt , a downstream signal of mitophagy, played a compensatory role in maintaining mitochondrial homeostasis in the case of mitophagy inhibition. Although UPR mt activation had no negative impact on mitophagy, UPR mt inhibition compromised the partial cardioprotective actions of mitophagy. This study shows how mitophagy modulates UPR mt to attenuate inflammation-related myocardial injury and suggests the potential application of mitophagy and UPR mt targeting in the treatment of myocardial stress.

show abstract

“…The study was approved by the Erasmus Medical Center Animal Experiments committee (Nrs. 17-2411-03 for animal 1 and 18-5224-01 for animal 2–4 35 ), and all methods were performed in accordance with relevant guidelines and regulations. Mean systolic aortic pressures of 101 mmHg, 77 mmHg and 82 mmHg were measured for pig 2, 3 and 4 respectively.…”

Section: Methodsmentioning

confidence: 99%

A direct comparison of natural and acoustic-radiation-force-induced cardiac mechanical waves

Keijzer

Caenen

Voorneveld

et al. 2020

Sci Rep

Self Cite

View full text Add to dashboard Cite

Natural and active shear wave elastography (SWE) are potential ultrasound-based techniques to non-invasively assess myocardial stiffness, which could improve current diagnosis of heart failure. This study aims to bridge the knowledge gap between both techniques and discuss their respective impacts on cardiac stiffness evaluation. We recorded the mechanical waves occurring after aortic and mitral valve closure (AVC, MVC) and those induced by acoustic radiation force throughout the cardiac cycle in four pigs after sternotomy. Natural SWE showed a higher feasibility than active SWE, which is an advantage for clinical application. Median propagation speeds of 2.5–4.0 m/s and 1.6–4.0 m/s were obtained after AVC and MVC, whereas ARF-based median speeds of 0.9–1.2 m/s and 2.1–3.8 m/s were reported for diastole and systole, respectively. The different wave characteristics in both methods, such as the frequency content, complicate the direct comparison of waves. Nevertheless, a good match was found in propagation speeds between natural and active SWE at the moment of valve closure, and the natural waves showed higher propagation speeds than in diastole. Furthermore, the results demonstrated that the natural waves occur in between diastole and systole identified with active SWE, and thus represent a myocardial stiffness in between relaxation and contraction.

show abstract

Perturbations in myocardial perfusion and oxygen balance in swine with multiple risk factors: a novel model of ischemia and no obstructive coronary artery disease

Cited by 36 publications

References 67 publications

RETRACTED: Molecular Perspectives of Mitophagy in Myocardial Stress: Pathophysiology and Therapeutic Targets

RETRACTED: Molecular Perspectives of Mitophagy in Myocardial Stress: Pathophysiology and Therapeutic Targets

Mitophagy coordinates the mitochondrial unfolded protein response to attenuate inflammation-mediated myocardial injury

A direct comparison of natural and acoustic-radiation-force-induced cardiac mechanical waves

Contact Info

Product

Resources

About