Molecular Signaling to Preserve Mitochondrial Integrity against Ischemic Stress in the Heart: Rescue or Remove Mitochondria in Danger

Cardiovascular diseases are one of the leading causes of death and global health problems worldwide, and ischemic heart disease is the most common cause of heart failure (HF). The heart is a high-energy demanding organ, and myocardial energy reserves are limited. Mitochondria are the powerhouses of the cell, but under stress conditions, they become damaged, release necrotic and apoptotic factors, and contribute to cell death. Loss of cardiomyocytes plays a significant role in ischemic heart disease. In response to stress, protective signaling pathways are activated to limit mitochondrial deterioration and protect the heart. To prevent mitochondrial death pathways, damaged mitochondria are removed by mitochondrial autophagy (mitophagy). Mitochondrial quality control mediated by mitophagy is functionally linked to mitochondrial dynamics. This review provides a current understanding of the signaling mechanisms by which the integrity of mitochondria is preserved in the heart against ischemic stress.

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New Insights Into the Role of Mitochondria Quality Control in Ischemic Heart Disease

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2021.774619 ◽

2021 ◽

Vol 8 ◽

Author(s):

Yanguo Xin ◽

Xiaodong Zhang ◽

Jingye Li ◽

Hui Gao ◽

Jiayu Li ◽

...

Keyword(s):

Quality Control ◽

Heart Disease ◽

Ischemic Heart Disease ◽

Molecular Mechanisms ◽

Ischemia Reperfusion Injury ◽

Mitochondrial Dynamics ◽

Ischemia Reperfusion ◽

Ischemic Heart ◽

Mortality And Morbidity ◽

Energy Deprivation

IHD is a significant cause of mortality and morbidity worldwide. In the acute phase, it's demonstrated as myocardial infarction and ischemia-reperfusion injury, while in the chronic stage, the ischemic heart is mainly characterised by adverse myocardial remodelling. Although interventions such as thrombolysis and percutaneous coronary intervention could reduce the death risk of these patients, the underlying cellular and molecular mechanisms need more exploration. Mitochondria are crucial to maintain the physiological function of the heart. During IHD, mitochondrial dysfunction results in the pathogenesis of ischemic heart disease. Ischemia drives mitochondrial damage not only due to energy deprivation, but also to other aspects such as mitochondrial dynamics, mitochondria-related inflammation, etc. Given the critical roles of mitochondrial quality control in the pathological process of ischemic heart disease, in this review, we will summarise the efforts in targeting mitochondria (such as mitophagy, mtROS, and mitochondria-related inflammation) on IHD. In addition, we will briefly revisit the emerging therapeutic targets in this field.

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High-Energy Phosphates and Ischemic Heart Disease: From Bench to Bedside

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2021.675608 ◽

2021 ◽

Vol 8 ◽

Author(s):

Hao Yi-Dan ◽

Zhao Ying-Xin ◽

Yang Shi-Wei ◽

Zhou Yu-Jie

Keyword(s):

Heart Disease ◽

Ischemic Heart Disease ◽

Critical Evaluation ◽

Basic Research ◽

High Energy ◽

Ischemic Heart ◽

High Energy Phosphates ◽

Term Survival ◽

Long Term Survival

The purpose of this review is to bridge the gap between clinical and basic research through providing a comprehensive and concise description of the cellular and molecular aspects of cardioprotective mechanisms and a critical evaluation of the clinical evidence of high-energy phosphates (HEPs) in ischemic heart disease (IHD). According to the well-documented physiological, pathophysiological and pharmacological properties of HEPs, exogenous creatine phosphate (CrP) may be considered as an ideal metabolic regulator. It plays cardioprotection roles from upstream to downstream of myocardial ischemia through multiple complex mechanisms, including but not limited to replenishment of cellular energy. Although exogenous CrP administration has not been shown to improve long-term survival, the beneficial effects on multiple secondary but important outcomes and short-term survival are concordant with its pathophysiological and pharmacological effects. There is urgent need for high-quality multicentre RCTs to confirm long-term survival improvement in the future.

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Abstract 12503: Synchrotron Radiation Coronary Microangiography for Evaluating Changes in the Caliber of the in vivo Rat Coronary Artery After Endothelin Administration

Circulation ◽

10.1161/circ.130.suppl_2.12503 ◽

2014 ◽

Vol 130 (suppl_2) ◽

Author(s):

Hiroaki Sakamoto ◽

Shonosuke Matsushita ◽

Kazuyuki Hyodo ◽

Chiho Tokunaga ◽

Fujio Sato ◽

...

Keyword(s):

Heart Disease ◽

Coronary Artery ◽

Synchrotron Radiation ◽

Regenerative Medicine ◽

Ischemic Heart Disease ◽

Coronary Arteries ◽

High Energy ◽

Ischemic Heart ◽

Density Resolution

Background: Conventional coronary angiography can visualize vessels of 300 μm in diameter, but not those of smaller diameter, such as the proliferating collateral arteries of ischemic heart disease and the new blood vessels formed in regenerative medicine. We have developed a system of synchrotron radiation coronary microangiography (SRCA) in the in vivo rat. The purpose of this study was to define the minimum detectable caliber change in the coronary arteries of the in vivo rat by inducing vasoconstriction with endothelin during SRCA. Method: SRCA was performed at the Photon Factory of the High Energy Accelerator Research Organization (Tsukuba, Japan). The advantages of synchrotron radiation derived X-rays are high spatial resolution (5 μm/pixel) due to increased photon density and straightness of beam. High density resolution is obtained with a high-gain avalanche rushing amorphous photoconductor camera using a fiber-optic plate. Rats were anesthetized. The polyethylene tube for angiography was inserted into the carotid artery. SRCA was performed before and after endothelin administration. Results: The electrocardiography showed ST elevation after endothelin administration. High spatial and density resolution images were obtained. Figures A and B show the changes in the caliber of the coronary arteries: Figure A shows the arteries before endothelin administration, and Figure B shows them after endothelin administration. The minimum identified coronary artery diameter in the in vivo rat was 65 μm, and the minimum detectable caliber change was 20 μm. Conclusion: The SRCA system could confirm the microvascular constriction of the coronary arteries in the in vivo rat after endothelin administration. We plan next to use SRCA to evaluate endothelial dysfunction in diabetic rats. SRCA may aid investigation of collateral artery proliferation in ischemic heart disease and new blood vessel formation in regenerative medicine in the near future.

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