**2. What happens during angioplasty?**

At the beginning, the doctor moves a guiding catheter into the artery with the blockage. Once the guiding catheter is in right place, a guide wire is moved across the blockage site and then a balloon catheter is moved to the blockage site. The balloon is inflated for a few seconds to compress the blockage against the artery wall and then the balloon is deflated. This proceeding can be repeated for a few times. Each time the balloon is pumped, the plaque widens a little more and enables the blood to flow through. If it is needed, a stent is placed within the coronary artery to keep the vessel open. Following this, the catheter is removed and the procedure is completed, as seen in Figure 1. As a result, the narrowed artery is enlarged by PTCA. PTCA is sometimes called coronary angioplasty. Coronary angioplasty has become increasingly popular as a result of its low morbidity and mortality and reduced hospital stay in comparison with surgery. Coronary angioplasty is generally effective and safe, but restenosis is frequent, occurring in about 30-40% of cases [2]. Restenosis limits the long-term beneficial effects of PTCA and related procedures. PTCA may be defined as the initial gain in artery lumen size, and restenosis can be defined as the loss of gain. Prevention of restenosis after successful PTCA remains one of the most challenging issues in the obstructive treatment of coronary artery disease [3].

## **3. What causes restenosis?**

As we mentioned above, stent placement is another option that is applied during angioplasty. Stent is a metallic scaffold that keeps the narrowed coronary artery portion open. Besides, as a metallic scaffold, the body may also perceive as alien. In fact, the trauma created by angio‐ plasty and stenting in tissue is more effective on restenosis. The trauma created by angioplasty and stenting leads cell stimulations in tissue, triggers cells in that region, and causes cell proliferation, migration, and thrombosis. Finally, cell movement and thrombosis lead to the renarrowing of the vessel.

Restenosis following balloon dilation of the vascular endothelium is thought to occur in three steps:

**Figure 1.** Balloon angioplasty and stent placement: (a) artery, (b) plaque formation, (c) balloon catheter at the blockage site, (d) balloon inflation and stent placement.


Over 1.5 million percutaneous coronary revascularization procedures are performed annually worldwide, most being intracoronary stenting. Clinically significant restenosis continues to occur in ˃14% of elderly patients within the first year undergoing PTCA. Therefore, there are great efforts for the prevention of restenosis [3]. For the prevention of restenosis, infusing a drug in solution at the site of injured artery is a simple approach and is not successful because of the rapid washout of infused drug from the arterial tissue. Almost 90% of infused drug is lost within 30 min with almost complete loss occurs in less than 24 h [5].
