Recent advances in inhibiting atherosclerosis and restenosis: from pathogenic factors, therapeutic molecules to nano-delivery strategies

Abstract

Due to dominant atherosclerosis etiology, cardiovascular diseases (CVDs) remain the leading cause of morbidity and mortality worldwide. In clinical trials, advanced atherosclerotic plaques can be removed by angioplasty and vascular...

Biomimicking Atherosclerotic Vessels: A Relevant and (Yet) Sub-Explored Topic

“…After being recruited to the intima, monocytes sequentially differentiate into macrophages and phagocytize oxidized low-density lipoproteins (LDL), forming foam cells [ 31 ]. Early atherosclerotic stages, considered reversible pathological changes [ 3 ], encompass these foam cells embedded in an extracellular matrix (ECM) with few inflammatory cells and fatty streaks. The progression of atherosclerosis is driven by the collagen density of ECM, as demonstrated by Garcia-Sabaté and colleagues [ 26 ].…”

“…Meanwhile, vascular smooth muscle cells (VSMCs) are activated and suffer a phenotypic transformation, migrating from media to intima and progressively thickening arterial walls. Hyperproliferative VSMCs lead to intimal hyperplasia and, together with the overproduction of matrix metalloproteinase via macrophages that degrades interstitial collagen, a fibrous plaque is formed [ 3 ]. Incorrect differentiation of VSMCs into osteoblasts occurs, and a mineralized matrix is generated in a process analogous to the bone formation mechanism.…”

“…Modifying lifestyle risk factors, combined with pharmacotherapy, is the well-accepted primary preventive measure [ 2 , 11 ]. Surgical interventions, however, are imperative when a lethal event is imminent, i.e., when atherosclerotic plaques are severely occluding blood vessels (stenosis higher than 75%), and it is crucial to restore blood supply [ 3 ]. Several interventional approaches can be accomplished depending on the plaque composition and stage severity [ 12 ]: (1) balloon angioplasty, consisting of a small balloon transported via a catheter that is inflated inside the stenotic artery to reopen the blocked area and reestablish the blood flow [ 13 ]; (2) atherectomy, which involves direct removal of plaque build-up in the arteries, using a device placed at the end of a catheter that could use directional, orbital or rotational, excisional or aspiration, or laser technologies to remove the atherosclerotic plaque efficiently [ 14 ]; or (3) vascular stenting, which is the insertion of stents (hollow and tubular structures) in the obstructed artery to open the blocked area, prevent re-blocking of vascular lumen, and support the artery wall at the same time [ 13 ].…”

Polo-like kinase 4 inhibitor CFI-400945 inhibits carotid arterial neointima formation but increases atherosclerosis

“…Thus, many strategies have been developed to target SMC proliferation. For example, several small molecule drugs, including rapamycin, paclitaxel, ceramide, doxorubicin, mRNA antagonists, and even siRNAs, have been tested for their anti-proliferative potential [ 6 ]. Still, none of them are satisfactory due to their limited therapeutic efficacies.…”

Improvement of Endothelial Cell-Polycaprolactone Interaction through Surface Modification via Aminolysis, Hydrolysis, and a Combined Approach

“…Te cellular compatibility of grafts is primarily determined by the surface properties, including morphology, topography, chemical structure, and functional groups [23,24]. Tese surface properties can be changed by multiple methods including treatment with drugs, peptides, growth factors, or adhesive proteins, or chemical reactions such as hydrolysis and aminolysis [15,[25][26][27][28][29][30][31]. Te advantage of chemical surface modifcation is the possibility of combining it with other treatments due to its simple and short procedural steps.…”