In this 2017 article, surgeon Axel Haverich argues that surgical and clinical observations—both his own and those of his colleagues—are more consistent with a view of atherosclerosis as “an adventitial microvessel disease” than the traditional understanding of atherosclerosis as a response to injury and/or inflammation in the arterial endothelium.
Haverich begins by recalling a 2016 coronary artery bypass grafting procedure, performed on a 67-year-old woman with calcified triple-vessel coronary artery disease, hypercholesterolemia, 42 pack-years of smoking, and arterial hypertension. He notes her atherosclerosis was not universal—the left radial artery showed no atherosclerosis, nor did the left internal mammary. Both vessels also showed thinner arterial walls and no visible vasa vasorum. Comparatively, the ascending aorta, epicardial coronary arteries, left anterior descending and right coronary arteries were calcified and highly vascularized. This was not unusual, as many surgeons take advantage of these variances in atherosclerosis to support coronary artery bypass operations:
My second assistant, however, a sixth-year medical student, started asking questions. Rightfully so! How can an artery showing severe proximal and distal sclerosis have, at its midpoint, a segment entirely free from disease with an infant-like wall structure? Why do the patient’s risk factors not affect the intramyocardial segment of her circumflex artery? How should the external muscle bridge prevent damage of the intima, the location thought to be where disease is initiated? As a long-term skeptic of intimal damage being the primary initiator of atherosclerosis, I brought to his attention the fact that areas predictably spared from atherosclerosis often lack VV.
With our observations and my sparse comments to the student still on my mind, I tried to develop a unifying theory. If a single mechanism like muscular coverage can protect a blood vessel wall against a plethora of atherosclerosis risk factors, perhaps there is an additional unrecognized pathophysiological mechanism that could account for the initiation of the disease process. This factor would need to involve the adventitia rather than the intima, because growing evidence supports an outside-in progression of disease development whereby vascular inflammation is initiated in the adventitia and is propagated inward toward the intima. The mechanism should also be able to precipitate the 2 major phenotypes of atherosclerosis, namely obstruction by plaques and aneurysmal dilatation.
Haverich unifies these observations with the theory that “blood vessel wall ischemia participates in the early stages of the process of atherosclerosis.” VV are not present in infants, and only become visible (and necessary) as arterial wall thickness increases with age. These VV are functional end arteries—that is, they are the only supply of nutrients to the tissues they reach. When the VV become obstructed or otherwise nonfunctional, then, vessel wall tissue becomes ischemic (i.e., lacks blood flow), and thus necrotic. Consequently, atherosclerosis could begin through dysfunction of these microvessels, rather than the large vessels (arteries) themselves; any disease in the arteries is secondary to damage in or to the VV.
This is supported by the observation that areas consistently spared of atherosclerosis also tend to lack VV. Haverich also argues this is more consistent with known risk factors for heart disease – hypertension, stress and smoking, for example, lack any direct links to an arterial view of atherosclerosis but are clearly contributors if the disease is primarily microvascular.