Figure 3.

Vascular remodeling in sickle cell disease (SCD)–associated pulmonary arterial hypertension (PAH) contributes to abnormal biomechanics. A, Upper panels of control and SCD-associated pulmonary arterial tissue samples after Movat’s pentachrome staining demonstrating increased neointimal formation. Representative sections are presented. M: vascular media; Adv: vascular adventitia; NI: neointima. Lower panels show control and SCD-associated pulmonary arterial samples after 2-photon second-harmonic-generation microscopy, wherein elastin is shown in green and collagen is shown in red. The white circle depicts clipped medial elastin; the single arrow points to inner media collagen deposition, and the double-arrow points to outer media collagen deposition and highlights clipping and fragmentation of media elastin and accumulation of collagen in the inner and outer regions of the vascular media of the SCD sample. B, Stress-versus-strain behavior of fresh SCD-associated pulmonary arterial compared with non-PAH control (CTRL) pulmonary arterial segment. ε_trans is the strain of transition from the elastin-dominant region (A) to the collagen-dominant region (B), associated with increased collagen engagement. C, Tissue-stored energy of fresh SCD-associated PAH pulmonary arterial segments compared with non-PAH control pulmonary arterial segments. PA: pulmonary arteries.