Cardiovascular function and structure are preserved despite induced ablation of BMP1-related proteinases.

Introduction: Bone morphogenetic protein 1 (BMP1) is part of an extracellular metalloproteinase family that biosynthetically processes procollagen molecules. BMP1- and tolloid-like (TLL1) proteinases mediate the cleavage of carboxyl peptides from procollagen molecules, which is a crucial step in fibrillar collagen synthesis. Ablating the genes that encode BMP1-related proteinases ( Bmp1 and Tll1 ) post-natally results in brittle bones, periodontal defects, and thin skin in conditional knockout (BTKO ) mice. Despite the importance of collagen to cardiovascular tissues and the adverse effects of Bmp1 and Tll1 ablation in other tissues, the impact of Bmp1 and Tll1 ablation on cardiovascular performance is unknown. Here, we investigated the role of Bmp1 - and Tll1 -ablation in cardiovascular tissues by examining ventricular and vascular structure and function in BTKO mice.

Methods: Ventricular and vascular structure and function were comprehensively quantified in BTKO mice (n=9) and in age- and sex-matched controls (n=9). Echocardiography, cardiac catheterization, and biaxial ex vivo arterial mechanical testing were performed to assess tissue function, and histological staining was used to measure collagen protein content.

Results: Bmp1 - and Tll1 -ablation resulted in maintained hemodynamics and cardiovascular function, preserved biaxial arterial compliance, and comparable ventricular and vascular collagen protein content.

Conclusions: Maintained ventricular and vascular structure and function despite post-natal ablation of Bmp1 and Tll1 suggests that there is an as-yet unidentified compensatory mechanism in cardiovascular tissues. In addition, these findings suggest that proteinases derived from Bmp1 and Tll1 post-natally have less of an impact on cardiovascular tissues compared to skeletal, periodontal, and dermal tissues.