Autophagy in Cardiovascular Disease Presentation

Seminar Presentation on Autophagy in Cardiovascular Disease

• Topic: Autophagy in Cardiovascular Disease
• Presenter: Smatt, Emmanuel Adeogoluwa
• Student ID: 21CA008178/2100223
• Department: Biochemistry

Outline

• Introduction: Covers autophagy and types of autophagy alongside the pathway
• Cardiovascular Diseases: Defines CVD, types, and autophagy within CVDs
• Roles of Autophagy: Details the role of autophagy in CVD
• Signaling pathways of Autophagy: Explaining signaling pathway roles in cardiovascular diseases.
• Therapeutic Approaches in Autophagy: Exploring the use of compounds such as metformin, resveratrol, etc. and microRNA modulation to target specific autophagy regulation pathways
• Conclusion & Recommendations: Summary of the role of autophagy in CVD and future research directions

Autophagy

• Autophagy is a conserved physiological process where cells transport their components to the lysosome for destruction via double-membrane vesicles called autophagosomes.
• It's a tightly regulated catabolic self-renewal system crucial for maintaining cellular homeostasis, handling stress, and initiating cellular renewal.
• Autophagy is essential for preventing cellular stresses, acting as a crucial quality control mechanism within the cell

Types of Autophagy

• Macroautophagy: The most studied type, involves the formation of autophagosomes that engulf damaged organelles and proteins for degradation in lysosomes
• Small autophagy (microautophagy): This process directly engulfs cytoplasmic material into lysosomes via lysosome membrane invagination, fostering selective and non-selective degradation.
• Chaperone-mediated autophagy (CMA): A highly selective process where substrate proteins are recognized by chaperones and translocated into the lysosome without forming vesicles

Autophagy Pathway

• Induction of autophagy and autophagosome formation depend on two primary protein complexes: ULK complex and the scaffold protein complex(RB1CC1/FIP200).
• Autophagy is crucial for cell survival under various stressful circumstances.
• However, uncontrolled autophagy can be harmful during reperfusion.

Cardiovascular Diseases

• Cardiovascular diseases (CVDs) are a group of disorders affecting the heart and blood vessels, including coronary heart disease, cerebrovascular disease, rheumatic heart disease, and others.
• Key behavioral risk factors for heart disease and stroke include unhealthy diet, physical inactivity, tobacco use, and harmful alcohol use.
• CVDs are the leading cause of death globally, with an estimated 17.9 million deaths annually.

Types of Cardiovascular Diseases

• Coronary artery disease (CAD/CHD): Characterized by reduced myocardial perfusion, leading to angina, myocardial infarction (MI) and/or heart failure.
• Cerebrovascular disease (CVD): Includes stroke and transient ischemic attack (TIA).
• Peripheral artery disease (PAD): Primarily affects the limbs, causing claudication.
• Aortic atherosclerosis: Involves thoracic and abdominal aneurysms.

Roles of Autophagy in Cardiovascular Diseases

• Autophagy plays a pivotal role in myocardial infarction by promoting cardiomyocyte survival through removing damaged mitochondria during ischemia/reperfusion.
• Autophagy's role in cardiac hypertrophy appears to be essential for maintaining cardiac structure and function, but it transforms into a maladaptive response under hemodynamic stress.
• Under doxorubicin-induced cytotoxicity, the restoration of autophagy flux and mitophagy is protective.

Signaling Pathways of Autophagy in Cardiovascular Diseases

• PI3K/Akt/mTOR: This pathway is crucial for regulating autophagy, with mTOR acting as a negative regulator under nutrient-rich conditions.
• AMPK/mTOR: AMPK activation promotes autophagy during energy stress by inhibiting mTOR.
• Nrf2/p62: Clearance of damaged proteins and organelles is facilitated by this pathway, leading to enhanced cellular protection.

Therapeutic Approaches in Autophagy

• Pharmacological Agents: Compounds like metformin, resveratrol, and trehalose can induce autophagy, reducing cardiac fibrosis and enhancing cardiac function.
• microRNA Modulation: Specific microRNAs, targeting autophagic regulation, show promise in enhancing autophagy, protecting cardiomyocytes, and promoting autophagosome formation.
• Caloric Restriction and Intermittent Fasting: These dietary interventions have been associated with augmented autophagic activity and mitigating age-related cardiovascular decline.

Therapeutic Approach in Autophagy (Cont'd)

• Inhibition of Autophagy (Specific Contexts): In certain cases, inhibiting excessive autophagy may be essential to prevent cell death and improve heart function, especially in doxorubicin-induced cardiotoxicity.

Conclusion

• Understanding the role of autophagy in cardiovascular diseases is vital for developing effective therapies.
• While autophagy demonstrates protective functions in specific contexts, its dysregulation can exacerbate the progression of cardiovascular disease.
• Future research should focus on fine-tuning and enhancing protective autophagic activity while mitigating potential harm.

This seminar presentation discusses the critical role of autophagy in cardiovascular diseases. It covers various types of autophagy, their pathways, and explores therapeutic approaches targeting autophagy regulation. The content provides insights into future research directions in the field of biochemistry.