Elastogenesis in Human Arterial Disease

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Abstract
Objective— Elastin, an extracellular matrix protein, constitutes about 30% of the dry weight of the arteries. Elastolysis induced by inflammatory processes is active in chronic arterial diseases. However, elastogenesis in arterial diseases has received little attention. In this work we hypothesized that disordered elastogenesis is active in matrix remodeling in atheroma and abdominal aortic aneurysm (AAA). Methods and Results— Human AAA and atheroma have 4- to 6-fold more tropoelastin protein than nondiseased arteries. The smooth muscle cell–containing media and fibrous cap of atherosclerotic arteries contain ordered mature elastin, whereas macrophage (MΦ)-rich regions often have disorganized elastic fibers. Surprisingly, in addition to smooth muscle cells, MΦs in diseased arteries also produce the elastin precursor tropoelastin, as shown by double immunostaining, in situ hybridization, and reverse transcription–polymerase chain reaction for tropoelastin mRNA. Cultured monocyte-derived MΦs can express the...