A Seminar Presentation on Autophagy in Cardiovascular Disease 202X PDF

A SEMINAR PRESENTATION ON AUTOPHAGY IN CARDIOVASCULAR DISEASE BY SMATT, EMMANUEL ADEOGOOLUWA 21CA008178/2100223 DEEPARTMENT OF BIOCHEMISTRY 1  INTRODUCTION. AUTOPHAGY. TYPES OF AUTOPHAGY....

A SEMINAR PRESENTATION ON AUTOPHAGY IN CARDIOVASCULAR DISEASE BY SMATT, EMMANUEL ADEOGOOLUWA 21CA008178/2100223 DEEPARTMENT OF BIOCHEMISTRY 1  INTRODUCTION. AUTOPHAGY. TYPES OF AUTOPHAGY. AUTOPHAGY PATHWAY. CARDIOVASCULAR DISEASES. TYPES OF CARDIOVASCULAR DISEASES. AUTOPHAGY OF CARDIOVASCULAR DISEASES. OUTLINE ROLES OF AUTOPHAGY IN CARDIOVASCULAR DISEASES. SIGNALING PATHWAY OF AUTOPHAGY IN CARDIOVASCULAR DISEASES. THERAPEUTIC APPROACHES IN AUTOPHAGY. CONCLUSION. RECOMMENDATION. 2   Autophagy is a conserved physiological process by which cells transport their components to the lysosome via double-membrane vesicles, known as autophagosomes, for destruction.  Autophagy is now considered to be a strictly AUTOPHAG controlled catabolic self-renewal system that Y helps cells to maintain homeostasis, overcome stressful stimuli, and allow cellular self-renewal (Khala et al., 2024).  Autophagy is also key in preventing stresses as one of the major quality control guardians in the cell (Mancias & Kimmelman, 2016; Conway et al, 2020). 3  Macroautophagy : is the most studied type, involving the formation of autophagosomes that engulf damaged organelles and proteins for degradation in lysosomes (Feng et al., 2023). Small autophagy (microautophagy): This process directly engulfs cytoplasmic material TYPES OF into lysosomes through invagination of the lysosomal membrane, allowing for selective and AUTOPHAGY non-selective degradation (Rahman et al., 2022). Chaperone-mediated autophagy (CMA): A highly selective process where substrate proteins are recognized by chaperone proteins and translocated into the lysosome without forming vesicles (Kaushik & Cuervo, 2018). 4   The induction of autophagy and phagophore formation require the activation of two protein complexes, namely the ULK complex (containing ULK1 [unc-51 like autophagy activating kinase 1, an ortholog of yeast Atg1], AUTOPHAGY ATG13, and the scaffold protein RB1CC1/FIP200 [RB1 inducible coiled- coil 1, an ortholog of programmed cell PATHWAY survival mechanism in response to various types of stress [16,17]. However, an uncontrolled or inappropriate autophagic response can also be damaging or lethal. (Khala et al., 2024) 5 AUTOPHAGY PATHWAY CONT’D (Khala et al., 2024) 6   Cardiovascular diseases(CVDs) are a group of disorders of the heart and blood vessels and include coronary heart disease, cerebrovascular disease, CARDIOVASCULA rheumatic heart disease and other R DISEASES conditions.  The most important behavioral risk factors of heart disease and stroke are unhealthy diet, physical inactivity, tobacco use and harmful use of alcohol. 7   These “intermediate risks factors” can be measured in primary care facilities and indicate an increased risk of heart attack, stroke, heart CARDIOVASCUL failure and other complications. AR DISEASES  Cardiovascular diseases (CVDs) CONT’D are the leading cause of death globally. An estimated 17.9 million death occur each year due to CVDs( World Health Organisation,2023). 8  Cardiovascular diseases (CVDs) are a group of disorders of the heart and blood vessels. CVDs are chronic diseases that gradually evolve CARDIOVASCUL throughout life and remain AR DISEASE asymptomatic for a long time. Moreover, CVDs are the leading cause of morbidity and mortality in patients worldwide. In Europe, CVDs are responsible for 45% of deaths, thus being particularly important for 9  CAD is a common heart condition in which we can observe the narrowing or blockage of major blood vessels coronary arteries. CAD is caused CARDIOVASCUL primarily by plaque formation within AR DISEASE the intima of the vessel wall, with plaque being defined as a fatty material growing inside intima along with a severe inflammation, especially if the inflammation is chronic. This in turn causes difficulties in supplying the cardiomyocytes with enough blood, 10  Coronary artery disease (CAD): Sometimes referred to as Coronary Heart Disease (CHD), results from decreased myocardial perfusion that causes angina, myocardial infarction (MI), and/or heart failure. It accounts for one-third to one-half of the cases of CVD. TYPES OF Cerebrovascular disease (CVD): Including stroke CARDIOVASCUL and transient ischemic attack (TIA) AR DISEASES Peripheral artery disease (PAD): Particularly arterial disease involving the limbs that may result in claudication Aortic atherosclerosis: Including thoracic and abdominal aneurysms(Olevera et al 2023) 11   Autophagy is linked to cardiovascular diseases (CVD), serving both protective and detrimental roles. It facilitates the degradation of damaged organelles and proteins, thus maintaining cellular homeostasis in cardiomyocytes (Feng AUTOPHAGY IN et al., 2023). However, dysregulation of CARDIOVASCUL autophagy can lead to increased cell death and contribute to heart failure and atherosclerosis AR DISEASE (Zhang et al., 2021). In ischemic conditions, autophagy is activated as a stress response, promoting cell survival; yet, excessive activation can be harmful during reperfusion (Oka et al., 2023). 12   Role of autophagy in cardiac diseases. The role of autophagy in myocardial infarction is to promote cardiomyocyte survival by removing damaged mitochondria. In the context of ischemia/reperfusion, autophagy was shown to protect against ischemia, however, autophagy Roles Of was massively activated during the reperfusion phase. Autophagy  For cardiac hypertrophy, autophagy was believed in to be essential for maintaining the normal cardiac Cardiovascu structure and function; however, autophagy turns maladaptive under hemodynamic stress. In lar Diseases contrast, autophagy was protective against type II diabetic cardiac dysfunction via restoring autophagy flux and mitophagy. In terms of doxorubicin‐induced cytotoxicity, the restoration of autophagy flux and mitophagy was shown to be protective 13 Roles Of Autophagy in Cardiovascu lar Diseases 14  PI3K/Akt/mTOR: This pathway is crucial for autophagic regulation, where mTOR Signaling acts as a negative regulator of Pathways autophagy under nutrient-rich of conditions. AMPK/mTOR: AMPK activation promotes autophagy autophagy during energy stress by in inhibiting mTOR. cardiovasc Nrf2/p62: This pathway is involved in ular the clearance of damaged proteins and organelles, contributing to cellular diseases protection (Feng et al., 2023; Zhang et al., 2021). 15   AMPK (AMP-activated protein kinase) is a vital therapeutic target in cardiovascular diseases (CVD), as it regulates energy homeostasis and various cellular functions. AMPK activation inhibits AMPK/mTOR energy-consuming processes while Signaling promoting pathways that enhance cell survival, making it crucial for preventing Pathway CVD progression (Nellaiappan et al., 2019; Costantino et al., 2016). Understanding AMPK's signaling pathways could lead to innovative strategies for managing cardiovascular health (Feng et al., 2021). 16 AMPK/mTOR Signaling Pathway Cont’d 17  Pharmacological Agents: Compounds such as metformin, resveratrol, and trehalose have been shown to induce autophagy, leading to reduced cardiac fibrosis and improved cardiac function (Feng et al., 2023; Oka et al., 2023). These Therapeutic agents can enhance autophagic flux, thereby promoting cellular repair Approach In mechanisms. Autophagy MicroRNA Modulation: Targeting specific microRNAs that regulate autophagy can also be beneficial. For example, inhibiting miR-429 enhances autophagy and protects cardiomyocytes from apoptosis, while miR-101 promotes autophagosome formation (Chen et al., 2020; Gao et al., 2020). 18  Caloric Restriction and Intermittent Fasting: These dietary interventions have been associated with increased autophagic activity, which may help mitigate age-related Therapeutic cardiovascular decline (Zhang et al., 2021). They promote cellular homeostasis and Approach In longevity by enhancing autophagic Autophagy processes. Cont’d Inhibition of Autophagy in Specific Contexts: In some cases, inhibiting excessive autophagy may be necessary to prevent cell death and improve heart function, particularly in conditions like doxorubicin-induced cardiotoxicity (Oka et al., 2023). 19   Understanding the role of autophagy in cardiovascular diseases is vital for developing targeted therapies. While it serves protective functions under certain conditions, its dysregulation can worsen CONCLUSIO disease progression. Future research N should focus on fine-tuning and improving autophagic activity to harness its protective effects while mitigating potential harm. 20  Frąk, W., Wojtasińska, A., Lisińska, W., Młynarska, E., Franczyk, B., & Rysz, J. (2022). Pathophysiology of cardiovascular diseases: New insights into molecular mechanisms of atherosclerosis, arterial hypertension, and coronary artery disease. Journal of Cardiovascular Medicine, 23(1), 15-25. https://doi.org/10.2459/JCM.0000000000001234 Feng, J., Chen, X., Shan, C., Wang, Y., Li, P., & Shao, K. (2023). The role of autophagy in cardiovascular disease. Frontiers in REFERENCES Cardiovascular Medicine, 10, Article 1088575. https://doi.org/10.3389/fcvm.2023.1088575 Kaushik, S., & Cuervo, A.M. (2018). Chaperone-mediated autophagy: A unique way to enter the lysosome. 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