Nitric oxide synthase and carotid artery plaque morphology
Journal: Atherosclerosis Supplements
Although the production and regulation of the isoforms of nitric oxide synthase (NOS) enzymes have been studied in several animals and cell types, there is little information about their production and role in the stabilisation or destabilisation of human atherosclerotic carotid artery plaques. Immunohistochemical techniques have been used to identify NOS isofonns present in echogenic (fibrous) and echolucent (lipid-laden) plaques, and to correlate their presence or absence with the preoperative ultrasonic appearances of the plaques. All carotid plaques showed a positive response to the presence of NOS enzymes irrespective of the predominant intraplaque features (i.e., fibrous or lipid). However, the observed level of inducible NOS (NOS-II) was higher in echolucent plaques than in echogenic plaques, whereas the level of neuronal constitutive NOS (NOS-I) was higher in echogenic than in echolucent plaques. Furthermore, there was no observed difference in the level of endothelial constitutive NOS (NOS-III). Since the activity of inducible form of NOS-II is known to be about lOOO-fold greater than the constitutive forms of NOS enzymes, this could be responsible for the expansive remodelling of the arterial wall. This reciprocal relationship between NOS-II and NOS-I might play an important role in (i) exposure of the lipid core of the plaque; (ii) rapture and ulceration of the fibrous cap; and (iii) haemorrhage and softening of the plaque making it more lipid-laden.
Any of these pathological events might destabilise the plaque, leading to embolisation and subsequent cerebrovascular events. The clinical application of these findings lies in identifying biochemical or immunological markers which can be measured in a surrogate tissue, such as blood, to identify patients at risk of developing the criteria for clinical intervention to prevent or reduce the risk of stroke.