Reducing residual cardiovascular risk: potential for nanotechnology
Even after intensive LDL-C lowering therapy, a significant residual risk persists in high risk patients.
Although there is a close interaction between inflammation and LDL-C, it is very likely that LDL-C lowering alone will not fully neutralize inflammation within the atherosclerotic lesions.
While anti-inflammatory treatments are a promising approach, there is also the risk of immunosuppression due to long-term systemic use. The use of highly selective and targeted therapies may help to overcome this limitation. Nanotechnology, which involves packaging of nanoparticles of therapeutic compounds, avoids the first pass clearance of a drug by the liver, and thus allows the compound to be delivered locally to non-hepatic tissues, including the atherosclerotic plaque. When conjugated with targeting ligands, nanoparticles can be directed to specific cells associated with plaque composition and the development and progression of atherosclerosis, such as macrophages.
The advantage of this approach over pharmacotherapy or monoclonal antibody therapy is that it allows high concentrations of the agent to be achieved locally in the plaque with low systemic concentrations, thereby improving therapeutic efficacy with less risk of side effects. Nanomedicine is already established in oncology and emerging research shows promise in the early diagnosis of buildup of plaque in arteries, as well as in monitoring its progression or disappearance (regression) following treatment.1,2
As inflammation associated with atherosclerosis is multifactorial in nature, there is also the possibility of detrimental effects. A recent study3 showed that a nanomedicine approach using liposomal nanoparticles loaded with the anti-inflammatory agent prednisolone led paradoxically to accelerated atherosclerosis, by promoting toxicity of the lipid-loaded macrophages. Further research is needed to close the gap between understanding atherosclerosis to the translation of targeted molecular tools.
According to Professor Erik Stroes (Academic Medical Center, Amsterdam, the Netherlands), one of the researchers in this field: 'Current approaches to treating cardiovascular disease by simply prescribing a statin for everyone will change dramatically within the next decade. Molecular imaging techniques and innovative novel therapeutic modalities - including local delivery strategies and selective anti-inflammatory interventions - highlight the need for personalized medicine in patients with cardiovascular disease. This is an exciting era with lots of challenges!'
Press release 84th European Atherosclerosis Society Congress, Innsbruck, Austria, May 30, 2016
1. Lobatto ME, Fuster V, Fayad ZA, Mulder WJM. Perspectives and opportunities for nanomedicine in the management of atherosclerosis. Nature Reviews Drug Discovery 2011;10:835-52.
2. Verweij SL, van der Valk FM, Stroes ES. Novel directions in inflammation as a therapeutic target in atherosclerosis. Curr Opin Lipidol 2015;26:580-5.
3. van der Valk FM, Schulte DM, Meiler S, Tang J, Zheng KH, Van den Bossche J, Seijkens T, Laudes M, de Winther M, Lutgens E, Alaarg A, Metselaar JM, Dallinga-Thie GM, Mulder WJM, Stroes ESG, Hamers AJA. Liposomal prednisolone promotes macrophage lipotoxicity in experimental atherosclerosis. Nanomedicine 2016;12:1463-70.