Chemical-induced, nonlethal, developmental model of dissecting aortic aneurysm

Abstract

This developmental model provides investigators an opportunity to explore the pathologic mechanisms of DAA and to examine the potential long-term effects of vascular remodeling of DAA.

Nonlinear imaging study of extracellular matrix in chemical‐induced, developmental dissecting aortic aneurysm: Evidence for defective collagen type III

“…Sacrifice times were at day GD20; a total of 40 fetuses from four treated and 44 fetuses from four control pregnant rats were used. Immunoblot studies of collagen type I, elastin, and FBN1 (the protein frequently defectively expressed in Marfan Syndrome) have been reported previously (Gong et al, 2006); hence, only collagen type III was addressed in the present study according to established methods (Yang et al, 2004).…”

“…Immunohistochemical staining was used to differentiate cells involved in the evolution or resolution of the DAAs observed, especially with respect to formation of the false lumen (vs. true, or original, aortic lumen), and to differentiate elastin and collagen subtypes in the aortic media and adventitia. Since our previous study (Gong et al, 2006)found no difference in biochemically measured total collagen and elastin, or in collagen type I immunostaining properties between control and pups from mothers exposed to semicarbazide, the present study focused on collagen type III, the second most plentiful collagen subtype in aorta, which is thought to be important in modulating and controlling fibrillogenesis of mature collagen (Niederreither et al, 1995; Fleischmajer et al, 1983, 1988; Gelman et al, 1979; Williams et al, 1978). Deparaffinized and rehydrated sections were incubated with anti‐CD31 (dilution: 1:5; Serotec, UK), antialpha smooth muscle cell actin monoclonal antibodies (dilution: 1:300; DakoCytomation), anti‐type I (dilution: 1:500) or type III (1:200) collagen antibodies (SouthernBiotech), and antielastin antibody (Cedarlaned, Canada), followed by staining by the labeled streptavidin‐biotin method with a Dako LSAB2 kit (KO684).…”

“…In initial experiments, timed‐pregnant Sprague‐Dawley rat dams were treated with either physiological saline (control, n = 7) or SSAO inhibitor semicarbazide at 6.13 mg/kg ( n = 10) by intraperitoneal injection daily on days 14 to 20 of gestation (average gestational time is 21 days). Doses were based on previously published data on the in vivo inhibition of SSAO (Gong et al, 2006; Langford et al, 1999), as the minimum dose effective at inducing DAA in 90% of pups from treated dams. All experiments were approved by the Animal Care and Use Committee, the University of Texas Medical Branch, Galveston, protocol #8812178.…”

“…In an earlier study, we found that in vivo inhibition of the vascular enzyme semicarbazide‐sensitive amine oxidase (SSAO) in rapidly growing weanling rats causes remarkable, specific deleterious effects on the development of the aorta (Langford et al, 2002). In more recent work, we described a developmental model of DAA in which pregnant rats (dams) given semicarbazide during the latter third of pregnancy give birth to newborns that exhibit arterial dissection with striking similarities to DAA in man (Gong et al, 2006). The role of SSAO in aortic media is relatively unknown, although it is of interest that a recent microarray study in humans found that the homologue to SSAO, membrane copper amine oxidase or vascular adhesion protein‐1, is downregulated in clinical dissecting ascending aortic aneurysms (Muller et al, 2002).…”

Murine model of surgically induced acute aortic dissection type A

“…Biglycans play a critical role in the control of collagen fibrillogenesis and in the proper assembly of the extracellular matrix. In utero exposure to semicarbazide, an inhibitor of the vascular enzyme semicarbazide-sensitive amine oxidase, results in newborn rats in thoracic aortic aneurysm and dissection, but no rupture [9]. The postnatal administration of β-aminopropionitrile monofumarate, which induces vascular medial degeneration, fragmentation of elastic fibers and apoptosis of vascular smooth muscle cells, leads to aortic dissection in rats by inhibiting the cross linking of collagen fibers [10].…”