Fibromuscular dysplasia pathophysiology: Difference between revisions

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==Overview==
==Overview==
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 [[Tunica intima|intima]], [[Tunica media|media]], or [[adventitia]] of the involved arteries; which ultimately lead to arterial narrowing. Despite numerous [[genetic]], [[hormonal]] and mechanical factors have been proposed, the [[etiology]] of fibromuscular dysplasia remains unknown.


==Pathophysiology==
==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 [[tunica intima|intima]], [[tunica media|media]], or [[adventitia]] of the involved arteries; which ultimately lead to arterial narrowing.
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 [[tunica intima|intima]], [[tunica media|media]], or [[adventitia]] of the involved arteries; which ultimately lead to arterial narrowing.
 


===Pathogenesis===
===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:
Despite numerous [[genetic]], [[hormonal]] and mechanical factors have been proposed, the [[etiology]] of fibromuscular dysplasia remains unknown. A variety of factors have been implicated. These include:
 
* Cigarette smoking and a history of [[hypertension]]<ref>{{Cite journal
1.Cigarette smoking and a history of [[hypertension]]<ref>{{Cite journal
  | author = [[C. N. Sang]], [[P. K. Whelton]], [[U. M. Hamper]], [[M. Connolly]], [[S. Kadir]], [[R. I. White]], [[R. Sanders]], [[K. Y. Liang]] & [[W. Bias]]
  | author = [[C. N. Sang]], [[P. K. Whelton]], [[U. M. Hamper]], [[M. Connolly]], [[S. Kadir]], [[R. I. White]], [[R. Sanders]], [[K. Y. Liang]] & [[W. Bias]]
  | title = Etiologic factors in renovascular fibromuscular dysplasia. A case-control study
  | title = Etiologic factors in renovascular fibromuscular dysplasia. A case-control study
Line 24: Line 23:
  | pmid = 2680961
  | pmid = 2680961
}}</ref>
}}</ref>
 
* Genetic factors, with a reported [[autosomal mode]] of [[inheritance]] in some families.<ref>{{Cite journal
2.Genetic factors with a reported autosomal mode of inheritance in some families.<ref>{{Cite journal
  | author = [[J. Perdu]], [[P. Boutouyrie]], [[C. Bourgain]], [[N. Stern]], [[B. Laloux]], [[E. Bozec]], [[M. Azizi]], [[C. Bonaiti-Pellie]], [[P.-F. Plouin]], [[S. Laurent]], [[A.-P. Gimenez-Roqueplo]] & [[X. Jeunemaitre]]
  | author = [[J. Perdu]], [[P. Boutouyrie]], [[C. Bourgain]], [[N. Stern]], [[B. Laloux]], [[E. Bozec]], [[M. Azizi]], [[C. Bonaiti-Pellie]], [[P.-F. Plouin]], [[S. Laurent]], [[A.-P. Gimenez-Roqueplo]] & [[X. Jeunemaitre]]
  | title = Inheritance of arterial lesions in renal fibromuscular dysplasia
  | title = Inheritance of arterial lesions in renal fibromuscular dysplasia
Line 37: Line 35:
  | pmid = 17330059
  | pmid = 17330059
}}</ref>
}}</ref>
*Some studies suggest fibromuscular dysplasia is a systemic disease with altered TGF-βexpression and connective tissue features
 
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.<ref>{{Cite journal
*Some studies suggest fibromuscular dysplasia is a systemic disease with altered [[TGF-β]] expression and [[connective tissue]] features.
 
* 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 but no association has been found     between fibromuscular dysplasia and previous use of oral contraceptives or abnormalities of endogenous sex hormones.<ref>{{Cite journal
  | author = [[C. N. Sang]], [[P. K. Whelton]], [[U. M. Hamper]], [[M. Connolly]], [[S. Kadir]], [[R. I. White]], [[R. Sanders]], [[K. Y. Liang]] & [[W. Bias]]
  | author = [[C. N. Sang]], [[P. K. Whelton]], [[U. M. Hamper]], [[M. Connolly]], [[S. Kadir]], [[R. I. White]], [[R. Sanders]], [[K. Y. Liang]] & [[W. Bias]]
  | title = Etiologic factors in renovascular fibromuscular dysplasia. A case-control study
  | title = Etiologic factors in renovascular fibromuscular dysplasia. A case-control study
Line 48: Line 48:
  | month = November
  | month = November
  | pmid = 2680961
  | pmid = 2680961
}}</ref>  
}}</ref>
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.
 
5.Mechanical factors due to  stretching of smooth muscle cells and microtrauma to the vessel wall


6.Ischemia due to fibrotic occlusion of the [[vasa Vasorum]]
* 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.
* Mechanical factors due to  stretching of [[smooth muscle cells]] and microtrauma to the vessel wall.
* [[Ischemia]] due to fibrotic occlusion of the [[vasa vasorum]].


==Genetics==
==Genetics==
*[[Genetic predisposition]] may play a role in the [[development]] of fibromuscular dysplasia. Owing to, FMD is more common among the first-degree relatives of patients with this condition.
*[[Genetic predisposition]] may play a role in the [[development]] of fibromuscular dysplasia. Owing to, 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,
*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.
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, about eight percent of patients report a confirmed diagnosis of FMD in one or more in first- or second-degree family members. However, the high prevalence of aneurysms, sudden death , and stroke 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.  
*In the US Registry, about eight percent of patients report a confirmed diagnosis of FMD in one or more in first- or second-degree family members. However, the high prevalence of aneurysms, sudden death, and stroke 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   
*Increased level of [[TGF]]1 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.
FMD patients also had elevated plasma levels of circulating [[TGF-β]]1 and [[TGF-β]]2 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.<ref>{{Cite journal
| author = [[Santhi K. Ganesh]], [[Rachel Morissette]], [[Zhi Xu]], [[Florian Schoenhoff]], [[Benjamin F. Griswold]], [[Jiandong Yang]], [[Lan Tong]], [[Min-Lee Yang]], [[Kristina Hunker]], [[Leslie Sloper]], [[Shinie Kuo]], [[Rafi Raza]], [[Dianna M. Milewicz]], [[Clair A. Francomano]], [[Harry C. Dietz]], [[Jennifer Van Eyk]] & [[Nazli B. McDonnell]]
| title = Clinical and biochemical profiles suggest fibromuscular dysplasia is a systemic disease with altered TGF-beta expression and connective tissue features
| journal = [[FASEB journal : official publication of the Federation of American Societies for Experimental Biology]]
| volume = 28
| issue = 8
| pages = 3313–3324
| year = 2014
| month = August
| doi = 10.1096/fj.14-251207
| pmid = 24732132
}}</ref>
   
*[[Polymorphisms]] of angiotensin-converting–enzyme allele ACE-I among patients with multifocal renal arterial fibromuscular
*[[Polymorphisms]] of angiotensin-converting–enzyme allele ACE-I among patients with multifocal renal arterial fibromuscular
dysplasia has been investigated.<ref>{{Cite journal
dysplasia has been investigated.<ref>{{Cite journal
Line 79: Line 89:
}}</ref>
}}</ref>


*In some case reports, the association of FMD with neurofibromatosis, Alport syndrome, and pheochromocytoma have been considered; Ans [[mutations]] in [[collagen]], and with [[alpha1-antitrypsin deficiency]] have also been suggested.
*In some case reports, the association of FMD with neurofibromatosis, Alport syndrome, and pheochromocytoma have been considered; And [[mutations]] in [[collagen]], and with [[alpha1-antitrypsin deficiency]] have also been suggested.<ref>{{Cite journal
| author = [[David P. Slovut]] & [[Jeffrey W. Olin]]
| title = Fibromuscular dysplasia
| journal = [[The New England journal of medicine]]
| volume = 350
| issue = 18
| pages = 1862–1871
| year = 2004
| month = April
| doi = 10.1056/NEJMra032393
| pmid = 15115832
}}</ref><ref>{{Cite journal
| author = [[G. Tromp]], [[Y. Wu]], [[D. J. Prockop]], [[S. L. Madhatheri]], [[C. Kleinert]], [[J. J. Earley]], [[J. Zhuang]], [[O. Norrgard]], [[R. C. Darling]] & [[W. M. Abbott]]
| title = Sequencing of cDNA from 50 unrelated patients reveals that mutations in the triple-helical domain of type III procollagen are an infrequent cause of aortic aneurysms
| journal = [[The Journal of clinical investigation]]
| volume = 91
| issue = 6
| pages = 2539–2545
| year = 1993
| month = June
| doi = 10.1172/JCI116490
| pmid = 8514866
}}</ref><ref>{{Cite journal
| author = [[W. I. Schievink]], [[F. B. Meyer]], [[J. E. Parisi]] & [[E. F. Wijdicks]]
| title = Fibromuscular dysplasia of the internal carotid artery associated with alpha1-antitrypsin deficiency
| journal = [[Neurosurgery]]
| volume = 43
| issue = 2
| pages = 229–233
| year = 1998
| month = August
| pmid = 9696074
}}</ref>


==Associated Conditions==
==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.
*The underlying [[connective tissue]] problem among [[arteries]] with FMD, causes weakening of [[arterial wall]] and leads to [[vessel]] [[dilatation]].The combined prevalence of aneurysms and FMD is estimated to be about 8%.
 
*FMD is a predisposing factor for spontaneous [[cervical carotid]], or renal artery  [[dissections]]. [[Dissection]] through the weakening of the arterial wall, in FMD are more commonly multiple than in patients without an identified underlying arteriopathy.


==Gross Pathology==
==Gross Pathology==
*On gross pathology, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
*On gross pathology, focal, irregular, thickening in medium and large muscular arteries are characteristic findings of FMD.


==Microscopic Pathology==
==Microscopic Pathology==
*On microscopic histopathological analysis, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
*On microscopic histopathological analysis, circumferential or eccentric deposition of collagen in intima but no lipid or inflammatory component are characteristic findings of FMD.
[[File:FMD..jpg||none|600px|thumb|Microscopic pathology Source:Librepathology]]


==References==
==References==

Latest revision as of 18:56, 30 August 2018

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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

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. Despite numerous genetic, hormonal and mechanical factors have been proposed, the etiology of fibromuscular dysplasia remains unknown.

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 of fibromuscular dysplasia remains unknown. A variety of factors have been implicated. These include:

  • Some studies suggest fibromuscular dysplasia is a systemic disease with altered TGF-β expression and connective tissue features.
  • 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 but no association has been found between fibromuscular dysplasia and previous use of oral contraceptives or abnormalities of endogenous sex hormones.[3]
  • 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.
  • Mechanical factors due to stretching of smooth muscle cells and microtrauma to the vessel wall.
  • Ischemia due to fibrotic occlusion of the vasa vasorum.

Genetics

  • Genetic predisposition may play a role in the development of fibromuscular dysplasia. Owing to, 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, about eight percent of patients report a confirmed diagnosis of FMD in one or more in first- or second-degree family members. However, the high prevalence of aneurysms, sudden death, and stroke 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-β1 and 2 secreted by fibroblasts in patients with FMD in comparison to matched

FMD patients also had elevated plasma levels of circulating TGF-β1 and TGF-β2 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.[4]

  • Polymorphisms of angiotensin-converting–enzyme allele ACE-I among patients with multifocal renal arterial fibromuscular

dysplasia has been investigated.[5]

Associated Conditions

  • FMD is a predisposing factor for spontaneous cervical carotid, or renal artery dissections. Dissection through the weakening of the arterial wall, in FMD are more commonly multiple than in patients without an identified underlying arteriopathy.

Gross Pathology

  • On gross pathology, focal, irregular, thickening in medium and large muscular arteries are characteristic findings of FMD.

Microscopic Pathology

  • On microscopic histopathological analysis, circumferential or eccentric deposition of collagen in intima but no lipid or inflammatory component are characteristic findings of FMD.
Microscopic pathology Source:Librepathology

References

  1. C. N. Sang, P. K. Whelton, U. M. Hamper, M. Connolly, S. Kadir, R. I. White, R. Sanders, K. Y. Liang & W. Bias (1989). "Etiologic factors in renovascular fibromuscular dysplasia. A case-control study". Hypertension (Dallas, Tex. : 1979). 14 (5): 472–479. PMID 2680961. Unknown parameter |month= ignored (help)
  2. J. Perdu, P. Boutouyrie, C. Bourgain, N. Stern, B. Laloux, E. Bozec, M. Azizi, C. Bonaiti-Pellie, P.-F. Plouin, S. Laurent, A.-P. Gimenez-Roqueplo & X. Jeunemaitre (2007). "Inheritance of arterial lesions in renal fibromuscular dysplasia". Journal of human hypertension. 21 (5): 393–400. doi:10.1038/sj.jhh.1002156. PMID 17330059. Unknown parameter |month= ignored (help)
  3. C. N. Sang, P. K. Whelton, U. M. Hamper, M. Connolly, S. Kadir, R. I. White, R. Sanders, K. Y. Liang & W. Bias (1989). "Etiologic factors in renovascular fibromuscular dysplasia. A case-control study". Hypertension (Dallas, Tex. : 1979). 14 (5): 472–479. PMID 2680961. Unknown parameter |month= ignored (help)
  4. Santhi K. Ganesh, Rachel Morissette, Zhi Xu, Florian Schoenhoff, Benjamin F. Griswold, Jiandong Yang, Lan Tong, Min-Lee Yang, Kristina Hunker, Leslie Sloper, Shinie Kuo, Rafi Raza, Dianna M. Milewicz, Clair A. Francomano, Harry C. Dietz, Jennifer Van Eyk & Nazli B. McDonnell (2014). "Clinical and biochemical profiles suggest fibromuscular dysplasia is a systemic disease with altered TGF-beta expression and connective tissue features". FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 28 (8): 3313–3324. doi:10.1096/fj.14-251207. PMID 24732132. Unknown parameter |month= ignored (help)
  5. A. Bofinger, C. Hawley, P. Fisher, N. Daunt, M. Stowasser & R. Gordon (2001). "Polymorphisms of the renin-angiotensin system in patients with multifocal renal arterial fibromuscular dysplasia". Journal of human hypertension. 15 (3): 185–190. doi:10.1038/sj.jhh.1001144. PMID 11317203. Unknown parameter |month= ignored (help)
  6. David P. Slovut & Jeffrey W. Olin (2004). "Fibromuscular dysplasia". The New England journal of medicine. 350 (18): 1862–1871. doi:10.1056/NEJMra032393. PMID 15115832. Unknown parameter |month= ignored (help)
  7. G. Tromp, Y. Wu, D. J. Prockop, S. L. Madhatheri, C. Kleinert, J. J. Earley, J. Zhuang, O. Norrgard, R. C. Darling & W. M. Abbott (1993). "Sequencing of cDNA from 50 unrelated patients reveals that mutations in the triple-helical domain of type III procollagen are an infrequent cause of aortic aneurysms". The Journal of clinical investigation. 91 (6): 2539–2545. doi:10.1172/JCI116490. PMID 8514866. Unknown parameter |month= ignored (help)
  8. W. I. Schievink, F. B. Meyer, J. E. Parisi & E. F. Wijdicks (1998). "Fibromuscular dysplasia of the internal carotid artery associated with alpha1-antitrypsin deficiency". Neurosurgery. 43 (2): 229–233. PMID 9696074. Unknown parameter |month= ignored (help)

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