Role of Heparanase Inhibition in Atherosclerosis Prevention. A Potential Novel Therapeutic Strategy

Atherosclerosis-Knowledge and PathogenesisAtherosclerosis (AS) is the process in which lipid particles, mainly oxidized LDL (Ox-LDL) accumulate in the luminal side of the arterial walls, then enclosed with a fibrous cap, which is composed of hypertrophic endothelial cells, collagen and extra-cellular matrix (ECM) proteins.Together, the lipid core and the surrounding fibrous cap form the atherosclerotic plaques, which cause progressive narrowing of the arterial lumen, resulting in impaired blood flow and oxygen supply, leading to ischemic injury in the affected organs [1].Being a multifactorial process, AS is accelerated in the presence of several cardiovascular risk factors, such as diabetes mellitus, hypertension, hyperlipidemia, complex genetic susceptibility to the disease, and tobacco abuse.In these diseases, higher levels of oxidative stress (OS) occur frequently, which lead to advanced disease and a higher rate of target organ damage and diseaserelated complications.OS augments the inflammatory response in the vascular endothelium, which results in vascular endothelial structural and functional damage, thus leading to accelerated AS [2,3].A proof for the role of OS in the progression of AS is that multiple endogenous and exogenous antioxidants had been proven to attenuate AS progression [4][5][6].Heparan sulfate proteoglycans (HSPGs) are macromolecules that are composed of glycosaminoglycan chains covalently bound to a protein core and are either embedded in cell membranes or located in the ECM [7].HSPGs exert important functions in cell-ECM interaction [8-10] and play key roles both in normal biologic processes [11][12][13][14][15][16]