Thoracic aortic aneurysm pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aarti Narayan, M.B.B.S [2]

Overview

An aneurysm occurs when a part or entire circumference of the vessel is pathologically dilated. A true aneurysm involves all three layers of the vessel, whereas pseudoaneurysm is characterized by disruption of the intima and media, and the dilated segment of the aorta is lined by adventitia alone. Thoracic aortic aneurysm (TAA) is a clinically silent and potentially fatal disease whose pathophysiology is poorly understood. Application of data derived from animal models and human tissue analysis of abdominal aortic aneurysms may prove misleading given current evidence of structural and biochemical aortic heterogeneity above and below the diaphragm. Genetic predisposition is more common in TAA and includes multi-faceted syndromes such as Marfan, Loeys-Dietz, and type IV Ehlers-Danlos as well as autosomal-dominant familial patterns of inheritance. Investigation into the consequences of these known mutations has provided insight into the cell signaling cascades leading to degenerative remodeling of the aortic medial extracellular matrix (ECM) with TGF-β playing a major role. Targeted research into modifying the upstream regulation or downstream effects of the TGF-β1 pathway may provide opportunities for intervention to attenuate TAA progression.

Pathophysiology

  • The clinical manifestations of thoracic aortic aneurysms depends on hemo-dynamic factors as well as factors intrinsic to individual arterial components.
  • Cystic medial necrosis is the most common pathology associated with ascending aortic aneurysms, whereas atherosclerosis is most frequently involved in the arch and descending aorta.
  • The aortic aneurysms associated with marfan syndrome grow at a faster rate and are more prone to rupture.
  • Most thoracic aneurysms are asymptomatic. However, the enlarging aorta can compress adjacent organs and cause symptoms like chest pain, dyspnea, hoarseness of voice, cough and dysphagia. Also symptoms of congestive heart failure can occur from severe aortic regurgitation and congestion of head, neck and upper extremities from superior vena cava compression.[1][2]

Elastin and Collagen

  • Increased activity of certain enzymes causes degradation of elastin and collagen in the arteries. This leads to loss of elasticity, weakens the aortic wall and causes it to dilate.[3]
  • Moreover, the part of aorta below the origin of renal arteries has less amount of elastin compared to collagen, accounting for increased frequency of aneurysms in this area[4].
  • In patients with marfan's syndrome there is a defect on chromosome 15 that is associated with impaired fibrillin synthesis, which is the core protein of microfibrils. Frequently among patients with marfan's syndrome there is cystic medial degeneration[5].

Hemodynamic Factors

  • The aorta being a low resistance circuit, repeated trauma from a reflected wave results in dilatation[6].
  • Systemic hypertension accelerates the process of dilatation of aorta and contributes to the formation of aneurysms[7][8][9].

Genetics


Pathogenesis

  • During embryologic development, the ascending and arch aorta to the ligamentum arteriosum formed by cells from the neural crest, and the media.
  • It grows by assembling sequential lamellar units to reach a total of 55-60 by adulthood.
  • It always maintaining a constant ratio of aortic diameter to medial thickness.
  • Interestingly, that ratio remains consistent during abdominal aortic growth as well, but in that region the precursor cells originate in the mesoderm and the number of lamellar units remains constant while the thickness of each unit is expanded during maturation.
  • This disparity in aortic cellular origin and segmental growth patterns contributes to differences in and extracellular matrix (ECM) microfibril density and VSMC reactivity to vasoactive growth factors , with downstream effects on susceptibility to aneurysmal degeneration.


Gross Pathology

Images shown below are courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology

Microscopic Pathology

On microscopic histopathological analysis, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].





















References

  1. Coady MA, Rizzo JA, Elefteriades JA (November 1999). "Developing surgical intervention criteria for thoracic aortic aneurysms". Cardiol Clin. 17 (4): 827–39. doi:10.1016/s0733-8651(05)70118-1. PMID 10589349.
  2. Ruddy JM, Jones JA, Spinale FG, Ikonomidis JS (November 2008). "Regional heterogeneity within the aorta: relevance to aneurysm disease". J. Thorac. Cardiovasc. Surg. 136 (5): 1123–30. doi:10.1016/j.jtcvs.2008.06.027. PMC 2679174. PMID 19026791.
  3. Castellano JM, Kovacic JC, Sanz J, Fuster V (April 2012). "Are we ignoring the dilated thoracic aorta?". Ann. N. Y. Acad. Sci. 1254: 164–74. doi:10.1111/j.1749-6632.2012.06493.x. PMID 22548582.
  4. Wolinsky H (October 1970). "Comparison of medial growth of human thoracic and abdominal aortas". Circ. Res. 27 (4): 531–8. doi:10.1161/01.res.27.4.531. PMID 5507030.
  5. Halloran BG, Davis VA, McManus BM, Lynch TG, Baxter BT (July 1995). "Localization of aortic disease is associated with intrinsic differences in aortic structure". J. Surg. Res. 59 (1): 17–22. doi:10.1006/jsre.1995.1126. PMID 7630123.
  6. Steed MM, Tyagi SC (October 2011). "Mechanisms of cardiovascular remodeling in hyperhomocysteinemia". Antioxid. Redox Signal. 15 (7): 1927–43. doi:10.1089/ars.2010.3721. PMC 3159179. PMID 21126196.
  7. Zhou J, Austin RC (2009). "Contributions of hyperhomocysteinemia to atherosclerosis: Causal relationship and potential mechanisms". Biofactors. 35 (2): 120–9. doi:10.1002/biof.17. PMID 19449439.
  8. Steed MM, Tyagi N, Sen U, Schuschke DA, Joshua IG, Tyagi SC (September 2010). "Functional consequences of the collagen/elastin switch in vascular remodeling in hyperhomocysteinemic wild-type, eNOS-/-, and iNOS-/- mice". Am. J. Physiol. Lung Cell Mol. Physiol. 299 (3): L301–11. doi:10.1152/ajplung.00065.2010. PMC 2951073. PMID 20581102.
  9. Dalton ML, Gadson PF, Wrenn RW, Rosenquist TH (July 1997). "Homocysteine signal cascade: production of phospholipids, activation of protein kinase C, and the induction of c-fos and c-myb in smooth muscle cells". FASEB J. 11 (8): 703–11. doi:10.1096/fasebj.11.8.9240971. PMID 9240971.
  10. Jones JA, Barbour JR, Lowry AS, Bouges S, Beck C, McClister DM, Mukherjee R, Ikonomidis JS (December 2006). "Spatiotemporal expression and localization of matrix metalloproteinas-9 in a murine model of thoracic aortic aneurysm". J. Vasc. Surg. 44 (6): 1314–21. doi:10.1016/j.jvs.2006.07.042. PMC 1761919. PMID 17145436.
  11. Rateri DL, Howatt DA, Moorleghen JJ, Charnigo R, Cassis LA, Daugherty A (September 2011). "Prolonged infusion of angiotensin II in apoE(-/-) mice promotes macrophage recruitment with continued expansion of abdominal aortic aneurysm". Am. J. Pathol. 179 (3): 1542–8. doi:10.1016/j.ajpath.2011.05.049. PMC 3157213. PMID 21763672.

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