Lysosomal Stress in Cardiovascular Diseases: Therapeutic Potential of Cardiovascular Drugs and Future Directions
Lysosomal dysfunction has emerged as a central contributor to the pathogenesis of cardiovascular diseases (CVDs), particularly due to its involvement in chronic inflammation, lipid dysregulation, and oxidative stress. This review highlights the multifaceted roles of lysosomes in CVD pathophysiology,...
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MDPI AG
2025-04-01
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| author | Toshiki Otoda Ken-ichi Aihara Tadateru Takayama |
| author_facet | Toshiki Otoda Ken-ichi Aihara Tadateru Takayama |
| author_sort | Toshiki Otoda |
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| description | Lysosomal dysfunction has emerged as a central contributor to the pathogenesis of cardiovascular diseases (CVDs), particularly due to its involvement in chronic inflammation, lipid dysregulation, and oxidative stress. This review highlights the multifaceted roles of lysosomes in CVD pathophysiology, focusing on key mechanisms such as NLRP3 inflammasome activation, TFEB-mediated autophagy regulation, ferroptosis, and the role of apolipoprotein M (ApoM) in preserving lysosomal integrity. Additionally, we discuss how impaired lysosomal acidification, mediated by V-ATPase, contributes to lipid-induced cardiac dysfunction. Therapeutically, several pharmacological agents, such as statins, SGLT2 inhibitors, TRPML1 agonists, resveratrol, curcumin, and ferroptosis modulators (e.g., GLS1 activators and icariin), have demonstrated promise in restoring lysosomal function, enhancing autophagic flux, and reducing inflammatory and oxidative injury in both experimental models and early clinical settings. However, key challenges remain, including limitations in drug delivery systems, the absence of lysosome-specific biomarkers, and insufficient clinical validation of these strategies. Future research should prioritize the development of reliable diagnostic tools for lysosomal dysfunction, the optimization of targeted drug delivery, and large-scale clinical trials to validate therapeutic efficacy. Incorporating lysosome-modulating approaches into standard cardiovascular care may offer a new precision medicine paradigm for managing CVD progression. |
| format | Article |
| id | doaj-art-e71c7b9f44354bab9a889fce0c17a12e |
| institution | DOAJ |
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| language | English |
| publishDate | 2025-04-01 |
| publisher | MDPI AG |
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| spelling | doaj-art-e71c7b9f44354bab9a889fce0c17a12e2025-08-20T03:14:32ZengMDPI AGBiomedicines2227-90592025-04-01135105310.3390/biomedicines13051053Lysosomal Stress in Cardiovascular Diseases: Therapeutic Potential of Cardiovascular Drugs and Future DirectionsToshiki Otoda0Ken-ichi Aihara1Tadateru Takayama2Division of General Medicine, Department of Internal Medicine, Nihon University School of Medicine, 30-1 Oyaguchikamicho, Itabashi, Tokyo 173-8610, JapanDepartment of Community Medicine and Medical Science, Tokushima University Graduate School of Biomedical Sciences, 3-18-15, Kuramoto-cho, Tokushima 770-8503, JapanDivision of General Medicine, Department of Internal Medicine, Nihon University School of Medicine, 30-1 Oyaguchikamicho, Itabashi, Tokyo 173-8610, JapanLysosomal dysfunction has emerged as a central contributor to the pathogenesis of cardiovascular diseases (CVDs), particularly due to its involvement in chronic inflammation, lipid dysregulation, and oxidative stress. This review highlights the multifaceted roles of lysosomes in CVD pathophysiology, focusing on key mechanisms such as NLRP3 inflammasome activation, TFEB-mediated autophagy regulation, ferroptosis, and the role of apolipoprotein M (ApoM) in preserving lysosomal integrity. Additionally, we discuss how impaired lysosomal acidification, mediated by V-ATPase, contributes to lipid-induced cardiac dysfunction. Therapeutically, several pharmacological agents, such as statins, SGLT2 inhibitors, TRPML1 agonists, resveratrol, curcumin, and ferroptosis modulators (e.g., GLS1 activators and icariin), have demonstrated promise in restoring lysosomal function, enhancing autophagic flux, and reducing inflammatory and oxidative injury in both experimental models and early clinical settings. However, key challenges remain, including limitations in drug delivery systems, the absence of lysosome-specific biomarkers, and insufficient clinical validation of these strategies. Future research should prioritize the development of reliable diagnostic tools for lysosomal dysfunction, the optimization of targeted drug delivery, and large-scale clinical trials to validate therapeutic efficacy. Incorporating lysosome-modulating approaches into standard cardiovascular care may offer a new precision medicine paradigm for managing CVD progression.https://www.mdpi.com/2227-9059/13/5/1053lysosomal stressstatinstranscription factor EBglutaminase 1senescenceNLRP3 inflammasome |
| spellingShingle | Toshiki Otoda Ken-ichi Aihara Tadateru Takayama Lysosomal Stress in Cardiovascular Diseases: Therapeutic Potential of Cardiovascular Drugs and Future Directions Biomedicines lysosomal stress statins transcription factor EB glutaminase 1 senescence NLRP3 inflammasome |
| title | Lysosomal Stress in Cardiovascular Diseases: Therapeutic Potential of Cardiovascular Drugs and Future Directions |
| title_full | Lysosomal Stress in Cardiovascular Diseases: Therapeutic Potential of Cardiovascular Drugs and Future Directions |
| title_fullStr | Lysosomal Stress in Cardiovascular Diseases: Therapeutic Potential of Cardiovascular Drugs and Future Directions |
| title_full_unstemmed | Lysosomal Stress in Cardiovascular Diseases: Therapeutic Potential of Cardiovascular Drugs and Future Directions |
| title_short | Lysosomal Stress in Cardiovascular Diseases: Therapeutic Potential of Cardiovascular Drugs and Future Directions |
| title_sort | lysosomal stress in cardiovascular diseases therapeutic potential of cardiovascular drugs and future directions |
| topic | lysosomal stress statins transcription factor EB glutaminase 1 senescence NLRP3 inflammasome |
| url | https://www.mdpi.com/2227-9059/13/5/1053 |
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