Table 1.

Distinct Aortic Pathology Manifests at Different Grades of Elastin Deficiency

	Eln−/− mice	hBAC-mNULL mice	Eln+/− mice	hBAC-mHET mice
Elastin expression	0%	~30%	~50%	~80%
Lumen area	Markedly decreased	Moderately decreased	Mildly decreased	Mildly decreased
External diameter	NQ, appears decreased	Moderately decreased	Mildly decreased	Mildly decreased
Distensibility	NQ, appears decreased	Moderately decreased	Mildly decreased	Unchanged
Media thickness	NQ, appears increased	Moderately increased	Mildly decreased	Unchanged
Media area	Markedly increased	Unchanged	Mildly decreased	Unchanged
SMC number	Markedly increased	Unchanged	NQ, likely decreased	Unchanged
SMC differentiation	Moderately less	Unchanged	NQ, likely unchanged	Unchanged
References	10, 11, 32	this study, 16	7, 10, 12, 13, 16	this study, 16

The mechanisms of obstructive aortopathy in WS have been explored in various murine models of graded elastin deficiency. Lumen loss of the aorta may result from increased media thickness relative to aortic diameter, inward medial expansion driven by SMC hyperplasia, decreased circumferential growth, and reduced compliance. Decreased lumen area and reduced external diameter is common to all grades of elastin deficiency. Reduced distensibility associates with elastin expression ≤ 50%, increased medial thickness characterizes both moderate and severe elastin deficiency, whereas medial expansion, SMC hyperplasia, and SMC dedifferentiation are restricted to severe elastin deficiency alone. Of note, media thickness is mildly increased in haploinsufficient DD mice [15], and diminished compliance is evident in hBAC-mHET aortas at supraphysiological pressures [16]. NQ = not quantified, though conclusions are based on representative images or extrapolation from related variables.