Analysis of arterial intimal hyperplasia: review and hypothesis

Abstract

BackgroundDespite a prodigious investment of funds, we cannot treat or prevent arteriosclerosis and restenosis, particularly its major pathology, arterial intimal hyperplasia. A cornerstone question lies behind all approaches to the disease: what causes the pathology?HypothesisI argue that the question itself is misplaced because it implies that intimal hyperplasia is a novel pathological phenomenon caused by new mechanisms. A simple inquiry into arterial morphology shows the opposite is true. The normal multi-layer cellular organization of the tunica intima is identical to that of diseased hyperplasia; it is the standard arterial system design in all placentals at least as large as rabbits, including humans. Formed initially as one-layer endothelium lining, this phenotype can either be maintained or differentiate into a normal multi-layer cellular lining, so striking in its resemblance to diseased hyperplasia that we have to name it "benign intimal hyperplasia". However, normal or "benign" intimal hyperplasia, although microscopically identical to pathology, is a controllable phenotype that rarely compromises blood supply. It is remarkable that each human heart has coronary arteries in which a single-layer endothelium differentiates early in life to form a multi-layer intimal hyperplasia and then continues to self-renew in a controlled manner throughout life, relatively rarely compromising the blood supply to the heart, causing complications requiring intervention only in a small fraction of the population, while all humans are carriers of benign hyperplasia. Unfortunately, this fundamental fact has not been widely appreciated in arteriosclerosis research and medical education, which continue to operate on the assumption that the normal arterial intima is always an "ideal" single-layer endothelium. As a result, the disease is perceived and studied as a new pathological event caused by new mechanisms. The discovery that normal coronary arteries are morphologically indistinguishable from deadly coronary arteriosclerosis continues to elicit surprise.ConclusionTwo questions should inform the priorities of our research: (1) what controls switch the single cell-layer intimal phenotype into normal hyperplasia? (2) how is normal (benign) hyperplasia maintained? We would be hard-pressed to gain practical insights without scrutinizing our premises.

Computed Tomography of Aortic Wall Calcifications in Aortic Dissection Patients

“…Our findings are supported by previous work from pathologists both in humans and different animals including elephants, cows, dogs and kangaroos [12], [24], [25], [26]. In 1944 Blumenthal et al [27] studied the relation between age and the amount of calcium in the intima and media of 540 human aortic specimens.…”

Bacterial cellulose as a potential vascular graft: Mechanical characterization and constitutive model development

“…It has been shown that increases in wall cyclic stretch inhibit rat vascular SMCs proliferation and enhance apoptosis 21 and in another study by Sotoudeh et al 22 cyclic stretch was found to increase porcine VSMC apoptosis. The fact that overproliferation of SMCs is the main mechanism involved in IH development 23 suggests a strong link between the reduction in cyclic stretch due to low compliance of the grafts and the development of IH. On the other hand, several studies have shown the influence of compliance mismatch on hemodynamic factors.…”

Preoperative dietary restriction reduces intimal hyperplasia and protects from ischemia-reperfusion injury

“…These interventions carry high risk of complications during the peri-procedural period including IR injury. Furthermore, surgical treatments for occlusive arterial disease suffer from high failure rates in the longer term due to re-occlusive vascular wall adaptations largely from cell proliferation-driven intimal hyperplasia 1 . Although IR and IH occur on different time scales with respect to the surgical procedure and via different molecular mechanisms, they collectively lead to considerable morbidity and mortality, with mitigation strategies currently largely lacking for both.…”