Segmental Arterial Mediolysis: A Multiguised Vasospastic Arteriopathy with Collateral Mesangial Cell Hyperplasia and Cardiac Toxicity Generated by Norepinephrine and Hyperdense Adrenoceptors Alone or by Crosstalk with Other Pressor Agents

Abstract

Segmental arterial mediolysis (SAM), an uncommon vasospastic arteriopathy occurring in the muscular arteries innervated by the peripheral sympathetic nervous system, usually presents with catastrophic abdominal and retroperitoneal hemorrhages in elderly patients. SAM is initiated by the coupling of norepinephrine to plastically derived hyperdense foci of alpha-1 adrenergic receptors on the sarcolemma of arterial muscle. This ligand is created by stimuli signaled by iatrogenic sympathomimetic agonists, some beta-2 agonists, or an excessive release of adrenal catecholamines. Coupling of this ligand with cytoplasmic heterotrimeric Gq protein excessively signals a cascade of biochemical events generating two principal lesions of injurious-phase SAM—the shearing of the outer media from the adventitia and an overload of cytoplasmic calcium ions toxic to mitochondria causing mediolysis and/or apoptosis. The massive hemorrhages are caused by ruptured gap aneurysms created by the transmedial loss of the medial muscle. A norepinephrine-directed reparative response rapidly develops either resolving angiographic injurious lesions or creating a body of vascular disorders, the new guises of SAM with ischemic clinical profiles. These present in the epicardial, vertebral, intestinal, and retroperitoneal arteries, often in younger females as fibromuscular dysplasia, dissecting hematomas, and persistent aneurysms. Norepinephrine can crosstalk with other pressor agents to create SAM lesions—serotonin with idiopathic pulmonary hypertension and persistent pulmonary hypertension in the newborn, histamine in spontaneous coronary artery dissections with eosinophilia, and endothelin-1 in a field effect generated by SAM that creates venous fibromuscular dysplasia. Norepinephrine also participates in the collateral development of mesangial hyperplasia with focal segmental glomerulosclerosis and myocardial mediolysis and apoptosis in subjects with markedly elevated heart rates. Conclusion. Norepinephrine coupling with plastically elevated alpha-1 adrenoceptor or other pressor agents generates SAM, a histologically recognizable vasospastic arteriopathy, that with repair is transformed into several different standardized arterial diseases that alter SAM’s clinical profile from a hemorrhagic to an ischemic disorder.

Peculiar morphologic characteristics of adrenal veins and similarity to fibromuscular dysplasia of artery: implication of pathogenesis

“…In some areas intimal fibroplasia, myxoid and fibrinoid medial degenerations/necrosis were noted (Figure 4), and these features were mostly observed in adrenal cortical adenomas. These morphologic characteristics were consistent with segmental arterial mediolysis (SAM) which were also similar to acute atherosis of macrophage type of placental membranes described in preeclampsia [22, 24, 25]. In pheochromocytomas, the arteries were mostly thin walled with significant reduction of muscular wall thickness and areas of “blood lakes” without discernable luminal endothelial linings.…”

“…SAM is also a histologic term, and it has been described in many anatomic sites, but the majority of the literature was case report with various clinical complications and outcomes [18][19][20][21]. Pathogenesis of SAM appears related to vasospasm and adrenal hormones/adrenergic receptor distribution within the target tissue [22,23].…”

Hepatic segmental arterial mediolysis: A case report and brief literature review

“…Slavin et al, more specifically has mentioned that SAM can be described as a vasospastic arteriopathy that is triggered when norepinephrine binds with alpha‐1 adrenoceptor on the vessel walls. As the arteriopathy is repaired, it is converted into various standardized arterial diseases that change the clinical presentation of SAM from a hemorrhagic disorder to an ischemic one 12 . Moreover, one of the histologic hallmarks of SAM is absence of inflammatory cells 5,7 …”

“…As the arteriopathy is repaired, it is converted into various standardized arterial diseases that change the clinical presentation of SAM from a hemorrhagic disorder to an ischemic one. 12 Moreover, one of the histologic hallmarks of SAM is absence of inflammatory cells. 5,7 Most studies concur that SAM most commonly affects men aged 50-60.…”

“…The pathophysiology of SAM has been the topic of extensive study and is mainly guided by histologic findings. 5 , 7 , 12 It is theorized that development of vacuoles in the smooth muscle of the outer media of arterial walls (mediolysis) is the first step, followed by granulation tissue formation and fibrosis that leads to the eventual disappearance of the vacuole if rupture does not occur between these two steps. 5 , 7 Slavin et al, more specifically has mentioned that SAM can be described as a vasospastic arteriopathy that is triggered when norepinephrine binds with alpha‐1 adrenoceptor on the vessel walls.…”