Cyclodextrins: A New Frontier in Atherosclerosis Treatment

Introduction

Atherosclerosis, a progressive inflammatory disease characterized by the buildup of cholesterol-laden plaques in the arterial walls, is a leading cause of cardiovascular diseases (CVDs) such as coronary artery disease, stroke, and peripheral artery disease. Despite advancements in therapeutic strategies, CVDs remain the primary cause of mortality and morbidity worldwide. The quest for novel treatments continues, with cyclodextrins emerging as promising candidates in the fight against atherosclerosis.

Understanding Atherosclerosis

Atherosclerosis develops when low-density lipoprotein (LDL) particles infiltrate the intimal layer of susceptible arterial regions. These LDL particles undergo oxidative and enzymatic modifications, leading to their aggregation and retention within the arterial wall. Macrophages engulf these modified LDL particles, transforming into foam cells and contributing to plaque formation. The accumulated cholesterol in these plaques can crystallize, posing a risk for plaque rupture and subsequent cardiovascular events.

The Role of Cyclodextrins

Cyclodextrins are cyclic oligosaccharides derived from starch through enzymatic processes. Cyclodextrin has shown significant potential in interacting with and removing cholesterol. These molecules possess a hydrophobic cavity capable of encapsulating cholesterol, facilitating its extraction from both extracellular and intracellular stores.

Mechanism of Action

  1. Cholesterol Solubilization: β-cyclodextrin forms inclusion complexes with cholesterol, enhancing its solubility and removal from atherosclerotic plaques. This property is particularly beneficial in dissolving extracellular cholesterol crystals, which are resistant to conventional cholesterol-lowering therapies.

  2. Efflux Promotion: Cyclodextrins promote the efflux of free cholesterol from macrophage foam cells, preventing toxic cholesterol accumulation and subsequent crystallization within these cells. This action complements the physiological role of high-density lipoprotein (HDL) in cholesterol transport and plaque regression.

Recent Advances and Experimental Evidence

Research has demonstrated the efficacy of cyclodextrins in preclinical models. Experimental studies indicate that cyclodextrins can significantly reduce cholesterol content in atherosclerotic lesions, thus mitigating plaque progression and instability. These findings underscore the potential of cyclodextrins as adjunctive agents in atherosclerosis therapy.

  1. In Vitro Studies: Laboratory experiments have shown that cyclodextrins can effectively extract cholesterol from cultured cells, suggesting a direct therapeutic impact on cellular cholesterol metabolism.

  2. In Vivo Studies: Animal models of atherosclerosis treated with cyclodextrins exhibit reduced plaque cholesterol content and improved plaque stability. These results highlight the translational potential of cyclodextrins from bench to bedside.

Future Directions

The integration of cyclodextrins into clinical practice could revolutionize the management of atherosclerosis, particularly for patients with persistent residual risk despite aggressive lipid-lowering treatments. Current lipid-lowering therapies, including statins, ezetimibe, and PCSK9 inhibitors, primarily focus on reducing circulating LDL cholesterol levels. However, they often fall short in addressing cholesterol crystals within plaques.

Cyclodextrins, with their unique mechanism of cholesterol extraction, offer a complementary approach to existing therapies. Their use could enhance plaque stability, reduce the incidence of major adverse cardiovascular events, and ultimately improve patient outcomes.

Conclusion

Cyclodextrins represent a novel and promising therapeutic avenue in the ongoing battle against atherosclerosis. Their ability to dissolve cholesterol crystals and promote cholesterol efflux from foam cells positions them as valuable agents in the effort to reduce the burden of atherosclerotic cardiovascular diseases. Future clinical studies are warranted to fully elucidate their therapeutic potential and pave the way for their integration into standard atherosclerosis treatment protocols.

As research continues to uncover the multifaceted benefits of cyclodextrins, these molecules may well become a cornerstone in the next generation of cardiovascular therapeutics, offering new hope for millions affected by atherosclerosis worldwide.


By leveraging the cholesterol-binding properties of cyclodextrins, we can move closer to eradicating atherosclerosis and its devastating consequences. This innovative approach promises not only to advance our understanding of cholesterol management but also to significantly improve the quality of life for patients battling cardiovascular diseases.


Referenced from ScienceDirect - 
https://www.sciencedirect.com/science/article/abs/pii/S0163725820301509?via%3Dihub

(NOTE - Please be aware that there are many different types of cyclodextrins. We strongly advise against any self experiments. At the time of publishing this, Cavadex is the only cyclodextrin proven safe in the treatment of atherosclerosis in humans.) 

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