Stents by Abigail Sossen

Coronary Artery Disease and Risk Factors

Coronary artery disease is marked by a buildup of plaque in the coronary arteries. Plaque is composed of lipids/triglycerides, calcium deposits, white blood cells, and cellular debris. The buildup of plaque stimulates an immune response leading to the development of atherosclerotic lesions through a process known as atherosclerosis. Coronary arteries supply blood to the myocardium, which is the muscle responsible for pumping blood to the rest of the body. The occlusion of the coronary arteries can lead to angina (chest pain) and heart attack (myocardial infarction). Risk factors for the disease include:

• High LDL or “bad cholesterol” (triglycerides in the blood) • Low HDL or “good” cholesterol • High blood pressure (hypertension) • Smoking • Obesity • Lack of exercise • Stress • Diabetes • Poor diet • Sleep apnea • Depression • Family history

Atherosclerosis

Atherosclerosis is a process of endothelial dysfunction inside arteries leading to the formation of an atherosclerotic lesion. The buildup of plaque deposited by lipoproteins, stimulates division of endothelial cells. Smooth muscle cells migrate and proliferate releasing collagen and extracellular matrix. 80-90% of people over the age of 30 have some level of atherosclerosis Thrombosis is the resultant ruptured lesion (1)(2).

Genetics

The progression of coronary artery disease is about 40 to 60% based on genetic variables. 33 genetic variants have been linked to the development and progression of coronary artery disease most of which are SNPs (single nucleotide polymorphisms). Of these 33, 8 are related to lipid production, 2 are related to hypertension and 23 are still unknown. Most of these are non-protein coding sequences (introns) thought to be regulatory regions known as long noncoding RNAs (lncRNA). More genetic risk factors correlate to more aggressive and earlier onset coronary artery disease. A current research goal is to better understand the mechanisms by which these genetic variants lead to coronary artery disease development and progression. (3)(4)(5)

PTCA – Percutaneous Transluminal Coronary Angioplasty

PTCA procedure described in detail in previous wiki pages. Risks of PTCA include: Blood clot at insertion site or PCI treated site, Infection at insertion site, Chest pain (angina), Myocardial infarction due to acute rupture of PTCA treated vessel or thrombus leading to emergency open heart surgery. Allergic reaction to balloon material, radioactive dye, metal alloy (BMS) or drug or polymer coating (DES) (6)

Bare Metal Stents

Bare metal stents have been developed in three main designs. The coil, tubular mesh, and slotted tubes. The coil stents have been phased out but once consisted of a piece of stainless steel formed into a coil. The tubular mesh was successful consisting of wires forming a meshwork to form a tube. Most modern stents now follow the slotted tube design in which the strut design is cut using lasers. (7) Bare metal stents were once made out of only stainless steel, now cobalt chromium, titanium chromium, titanium nickel, nickel chromium and platinum chromium alloys have all been used successfully. Considerations when choosing a BMS -strut pattern/scaffolding and support/strength -thickness/ mass of metal -length and diameter -conformability/flexibility -radiopacity – ability to interfere with x-rays -thrombogenicity – tendency to form a thrombus -balloon overhang – can harm healthy endothelial lining -elastic recoil – natural tendency of stent to separate (slightly) from arterial wall immedietly following implantation -negative remodeling – uncontrolled endothelialization in response to stent/angioplasty, can lead to neointimal hyperplasia (scar tissue) and restenosis (7)

Drug Eluting Stents

Drug eluting stents were developed to lower the risk of restenosis, thrombosis, negative remodeling, and inflammation due to immune response to the presence of a bare metal stent. Drug eluting stents elute one of two major drugs (paclitaxel or sirolimus) which both act as cell cycle inhibitors to prevent proliferation and induce apoptosis. The stents are usually coated with a polymer that acts as a drug delivery agent, the drugs are slowly released for up to one year after the stent has been implanted. It has yet to be determined whether or not a bioresorbable polymer is good for drug delivery, because eventual contact between the metal and the blood will occur which may increase the risk for restenosis. (8)

 Paclitaxel binds to the cytoskeletal protein tubulin, interfering with the formation of a functional mitotic spindle, forcing the cell into apoptosis at the G1 checkpoint.  Sirolimus also known as rapamycin inhibits the mTOR (mammalian target of rapamycin) pathway, which also results in apoptosis.  (9)