Journal
FRONTIERS IN CARDIOVASCULAR MEDICINE
Volume 8, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fcvm.2021.689101
Keywords
diabetic cardiomyopathy; heart failure; Miro1; microtubules; HDAC6; NLRP3; mitochondrial dysfunction; mitochondrial movement
Categories
Funding
- British Heart Foundation [PG/18/61/33966]
- King Abdulaziz University
- Saudi Arabian Cultural Bureau (SACB)
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Both type 1 and type 2 diabetes can lead to heart failure through remodelling of the myocardium and abnormal cardiac bioenergetics associated with mitochondrial dysfunction. Factors such as mitochondrial shape, size, and organization within cardiomyocytes play a key role in influencing mitochondrial function. Inflammation may contribute to the development of heart failure and diabetes.
A pathophysiological consequence of both type 1 and 2 diabetes is remodelling of the myocardium leading to the loss of left ventricular pump function and ultimately heart failure (HF). Abnormal cardiac bioenergetics associated with mitochondrial dysfunction occurs in the early stages of HF. Key factors influencing mitochondrial function are the shape, size and organisation of mitochondria within cardiomyocytes, with reports identifying small, fragmented mitochondria in the myocardium of diabetic patients. Cardiac mitochondria are now known to be dynamic organelles (with various functions beyond energy production); however, the mechanisms that underpin their dynamism are complex and links to motility are yet to be fully understood, particularly within the context of HF. This review will consider how the outer mitochondrial membrane protein Miro1 (Rhot1) mediates mitochondrial movement along microtubules via crosstalk with kinesin motors and explore the evidence for molecular level changes in the setting of diabetic cardiomyopathy. As HF and diabetes are recognised inflammatory conditions, with reports of enhanced activation of the NLRP3 inflammasome, we will also consider evidence linking microtubule organisation, inflammation and the association to mitochondrial motility. Diabetes is a global pandemic but with limited treatment options for diabetic cardiomyopathy, therefore we also discuss potential therapeutic approaches to target the mitochondrial-microtubule-inflammatory axis.
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