Aim: 

Collagens XV and XVIII are structurally related basement membrane-associated proteoglycans, their highest degree of homology involving the C-terminal endostatin domain which has a role in controlling blood vessel formation and tumour growth. Our previous studies with knockout (KO) mice show that ColXV is needed for muscle and capillary integrity. Here we address the physiological significance of ColXV in KO mice in microvessels and the heart and the mechanisms whereby it supports the integrity of tissues.

Methods: 

The structure and vasculature of selected tissues were analyzed by light and electron microscopy. Cardiac function, intra-arterial blood pressure, microhemodynamics, and gene expression profiles were studied using echocardiography, telemetry, intravital microscopy, and PCR, respectively. Experimental hypertension was induced with angiotensin II or with a nitric oxide synthesis inhibitor.

Results: 

Under basal conditions, lack of Col XV resulted in increased permeability and impaired microvascular hemodynamics, distinct early-onset and aging-dependent defects in the heart structure and function, a poorly organized fibrillar collagen matrix with marked interstitial deposition of non-fibrillar protein aggregates, increased tissue stiffness, and irregularly organized cardiomyocytes. In response to experimental hypertension Col15a1 gene expression was increased in the left ventricle of WT mice, but mRNA expression of natriuretic peptides and ECM modeling were dysfunctional in KO mice. Lack of ColXV affected collagen fibril formation in several tissues.

Conclusions: 

Col XV is necessary for ECM organization in the heart and other tissues, and for the structure and functions of microvessels. Col XV deficiency leads to a complex cardiac phenotype, and predisposes the subject to pathological responses under cardiac stress.