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 fibri...
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Published in | Cellular and molecular bioengineering Vol. 11; no. 4; pp. 255 - 266 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
New York
Springer US
01.08.2018
Springer Nature B.V |
Subjects | |
Online Access | Get full text |
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Summary: | 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 (BT
KO
) 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 BT
KO
mice.
Methods
Ventricular and vascular structure and function were comprehensively quantified in BT
KO
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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Associate Editor Michael R. King oversaw the review of this article. |
ISSN: | 1865-5025 1865-5033 |
DOI: | 10.1007/s12195-018-0534-y |