Fibromuscular dysplasia pathophysiology
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Management of Patients With Fibromuscular Dysplasia of the Extracranial Carotid Arteries |
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mohsen Basiri M.D.
Overview
Pathophysiology
In Fibromuscular dysplasia, the proliferation of vascular smooth muscle of one or more small or medium-sized arteries undergo dysplasia and cause stenosis. this abnormal cellular development is characterized by fibrous thickening of the intima, media, or adventitia of the involved arteries; which ultimately lead to arterial narrowing.
Pathogenesis
- Despite numerous genetic, hormonal and mechanical factors have been proposed, the etiology fibromuscular dysplasia remains unknown. A variety of factors have been implicated. These include:
1)Cigarette smoking and a history of hypertension
. Sang CN, Whelton PK, Hamper UM, et al. Etiologic factors in renovascular fibromuscular dysplasia: a case-control study. Hypertension 1989;14:472-9.
2)Genetic factors with a reported autosomal mode of inheritance in some families
. Perdu J, Boutouyrie P, Bourgain C, et al. Inheritance of arterial lesions in
renal fibromuscular dysplasia. J Hum Hypertens 2007; 21:393.
. Ganesh SK, Morissette R, Xu Z, et al. Clinical and biochemical profiles
suggest fibromuscular dysplasia is a systemic disease with altered TGF-β
expression and connective tissue features. FASEB J 2014; 28:3313.
3) Hormonal influence, The increased incidence of FMD in women as compared with men suggests a possible hormonal given the predominance in women of childbearing age No association has been found between fibromuscular dysplasia and previous use of oral contraceptives or abnormalities of endogenous sex hormones.21 21. Sang CN, Whelton PK, Hamper UM, et al. Etiologic factors in renovascular fibromuscular dysplasia: a case-control study. Hypertension 1989;14:472-9. 4) Some authors have proposed the sex difference to be related to immune system functioning, but overt inflammation, as is observed in most classic autoimmune diseases, is histologically lacking. 4) Mechanical factors due to stretching of smooth muscle cells and microtrauma to the vessel wall
5) Ischemia due to fibrotic occlusion of the vasa Vasorum
Genetics
- Genetic predisposition may play a role in the development of fibromuscular dysplasia since, FMD is more common among the first-degree relatives of patients with this condition.
- Some studies showed an autosomal dominant transmission pattern for fibromuscular dysplasia. however, as of yet,
no etiologic genes have been identified for this disease. Applying molecular genetics investigations will reveal information about FMD pathogenesis, and family-based studies, evaluating genome of candidates, and wide genome studies can help to recognize pathophysiology of FMD.
In the US Registry, 7.3% of patients report a confirmed diagnosis of FMD in ≥1 first- or second-degree family members. 2 However, the high prevalence of aneurysms(23.5%), sudden death (19.8%), and stroke (53.5%) among first- and second-degree family members in the US Registry shows that FMD may be associated with systemic arteriopathy with a great diversity of clinical phenotype traits. It is hypothesized that FMD may have common features with vascular connective tissue diseases, such as Loeys-Dietz syndrome or the vascular type of Ehlers-Danlos syndrome.
increased level of TGF-b1 and 2 secreted by fibroblasts in patients with FMD in comparison to matched FMD patients also had elevated plasma levels of circulating TGF-b1 and TGF-b2 relative to matched controls. The potential involvement of TGF-b pathways in the pathogenesis of FMD is an area for future investigation, especially as this pathway could provide a potential target for disease-modifying medical therapies.
In case reports, FMD has been associated with mutations in collagen [20] , with cutis laxa [21] , and with alpha1-antitrypsin deficiency [22] . Associative links to neurofibromatosis, Alport syndrome, and pheochromocytoma have also been suggested. [2]
and among persons with the angiotensin-converting–enzyme allele ACE-I. 24 24. Bofinger A, Hawley C, Fisher P, Daunt N, Stowasser M, Gordon R. Polymorphisms of the renin-angiotensin system in patients with multifocal renal arterial fibromuscular dysplasia. J Hum Hypertens 2001;15:185-90.
Associated Conditions
Associated vascular pathologies In 1982, Mettinger and Ericson [14] scrutinized 4000 consecutively performed cerebral angiographies and found 37 that were consistent with FMD. Of these, 19 patients had aneurysms. In 1988, Cloft et al performed a meta-analysis including 498 FMD patients as well as examined 117 of their own patients and found a combined prevalence of aneurysms to be 7.3%. [15] In 1975, Stanley et al found that 8 of their 17 cerebrovascular FMD cases had intracranial aneurysms, and they proposed a classification system that includes a "medial fibroplasias with aneurysms" subtype. [11] The beadlike dilatations observed within FMD lesions share gross and histologic characteristics of aneurysms. The casual link between FMD and aneurysms is less clear but is possibly related to an underlying connective tissue problem that results in loss of arterial wall strength. This wall weakness may allow for vessel dilation (aneurysm formation and beading in FMD) as well as injury, which then causes compensatory fibroplasia. Besides aneurysms, many case series and reports have identified FMD in patients presenting with arterial dissection. [16, 17]
FMD lesions likely predispose the artery to dissection through weakening of the arterial wall. FMD is a predisposing factor in 15% of spontaneous cervical carotid dissections. Dissections in FMD are more commonly multiple than in patients without an identified underlying arteriopathy.
Gross Pathology
- On gross pathology, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
Microscopic Pathology
- On microscopic histopathological analysis, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].