Atherosclerosis is a form of arteriosclerosis characterized by presence of lesions called atheromas in the intima. Atheromatous plaques(atheromas) are lesions which are composed of lipid cores( mainly cholesterol and cholesterol esters and necrotic debris) covered by fibrous cap.
Major risk factor for atherosclerosis are: Genetics, age, gender, hyperlipidemia, diabetes mellitus, hypertension, cigarette smoking, hyperhomocysteinemia. Regarding development of atherogenesis there are two dominant theories: one based on repeated formation and organization of thrombi and the other focusing in intimal cellular proliferation in response to endothelial injury. The contemporary view incorporates elements of both theories. Based on the response to injury hypothesis atherosclerosis is considered as chronic inflammatory response of the arterial wall to endothelial injury. Progression of the lesion involves lipoproteins, macrophages, T lymphocytes, and cellular components of arterial wall.
Atherosclerotic plaques have three principal components:
1.cells (smooth muscle cells, macrophages, T cells)
2.extracellular matrix (collagen, elastic fibers, proteoglycans)
3. intracellular and extracellular lipids.
Major clinical consequences of atherosclerosis are:
1.myocardial infarction (heart attack)
2.cerebral infarction (stroke)
4.peripheral vascular disease (gangrene of extremities).
Latest studies are focused on targeting biodegradable nanoparticles (nano-“drones”) that deliver a special type of drug that enhances resolution of atherosclerotic plaques, making them more stable, thereby preventing heart attacks and stokes.
In this study, nanomedicines are designed to carry anti-inflammatory drugs, in this case Annexin A1.
Annexin A1 ( also known as lipocortin I) is a protein which inhibits phospholipase A2 activity.
In mouse models with advanced atherosclerosis, after 5 weeks treatment with nanomedicines the damage to the arteries was repaired and the plaques were more stable. Scientists observed a reduction of reactive oaxygen species ( ROS), increase of collagen synthesis and reduction of necrotic core.
Resolving inflammation through nanoparticles shows exciting potential for treatment of atherosclerosis and its consequences !!!