Article Impact Level: HIGH Data Quality: STRONG Summary of Nature Communications, 15(1), 10464. https://doi.org/10.1038/s41467-024-50753-8 Dr. Pratibha Singh et al.
Points
- Atherosclerotic plaques in type 2 diabetes patients show significantly reduced collagen and fibrous tissue compared to non-diabetic individuals, indicating impaired plaque stability.
- A deficiency in transforming growth factor-beta2 (TGF-β2) was identified in diabetic plaques, contributing to reduced fibrous repair markers and a higher risk of cardiovascular events.
- Elevated blood glucose levels correlate with decreased TGF-β2 activity and lower levels of protective proteins, weakening plaque integrity and increasing the risk of heart attack and stroke.
- Targeting TGF-β2 to enhance fibrous repair mechanisms may help stabilize plaques and mitigate cardiovascular risks in type 2 diabetes patients.
- The research will explore treatments to boost protective protein production or plaque stabilization, providing new strategies for managing cardiovascular disease in diabetes.
Summary
This study investigates the mechanisms underlying the increased risk of cardiovascular disease in individuals with type 2 diabetes, mainly focusing on alterations in fibrous repair processes within atherosclerotic plaques. Using data from the Carotid Plaque Imaging Project, the research team compared plaques from type 2 diabetes patients to those from non-diabetic patients, identifying a significant reduction in collagen levels in the plaques of diabetic patients. The study highlights a specific deficiency in transforming growth factor-beta2 (TGF-β2) in the plaques of diabetic patients, which is associated with a lack of fibrous repair markers and a higher risk of cardiovascular events. These findings suggest that TGF-β2 plays a crucial role in collagen formation and vascular smooth muscle cell differentiation in the aortic plaques, and its deficiency may contribute to the progression of cardiovascular disease in diabetes.
The research team analyzed a total of 219 atherosclerotic plaques, with 72 from type 2 diabetes patients, and found that plaques from these patients had lower levels of collagen and fibrous tissue compared to plaques from non-diabetic patients. Elevated blood glucose levels were shown to correlate with lower levels of protective proteins, which are essential for maintaining plaque integrity. Specifically, high blood sugar levels were linked to reduced TGF-β2 activity, impairing the ability to form protective connective tissue in the plaques, thereby increasing the risk of heart attack and stroke. These results emphasize the importance of glycemic control in preventing the progression of cardiovascular disease in type 2 diabetes.
The study’s findings suggest therapeutic strategies targeting TGF-β2-driven fibrous repair mechanisms may help mitigate cardiovascular risks in type 2 diabetes patients. Future research is expected to explore potential treatments that could enhance the production of protective proteins in atherosclerotic plaques or stabilize these plaques to reduce the likelihood of cardiovascular events. Such treatments may provide new avenues for improving the management of cardiovascular disease in patients with type 2 diabetes.
Link to the article: https://www.nature.com/articles/s41467-024-50753-8
References Singh, P., Sun, J., Cavalera, M., Al-Sharify, D., Matthes, F., Barghouth, M., Tengryd, C., Dunér, P., Persson, A., Sundius, L., Nitulescu, M., Bengtsson, E., Rattik, S., Engelbertsen, D., Orho-Melander, M., Nilsson, J., Monaco, C., Goncalves, I., & Edsfeldt, A. (2024). Dysregulation of MMP2-dependent TGF-ß2 activation impairs fibrous cap formation in type 2 diabetes-associated atherosclerosis. Nature Communications, 15(1), 10464. https://doi.org/10.1038/s41467-024-50753-8
