Fibrillar, Fibril-associated and Basement Membrane Collagens of the Arterial Wall: Architecture, Elasticity and Remodeling Under Stress

Abstract

The ability of a human artery to pass through 150 million liters of blood sustaining 2 billion pulsations of blood pressure with minor deterioration depends on unique construction of the arterial wall. Viscoelastic properties of this construction enable to re-seal the occuring damages apparently without direct immediate participance of the constituent cells. Collagen structures are considered to be the elements that determine the mechanoelastic properties of the wall in parallel with elastin responsible for elasticity and resilience. Collagen scaffold architecture is the function-dependent dynamic arrangement of a dozen different collagen types composing three distinct interacting forms inside the extracellular matrix of the wall. Tightly packed molecules of collagen types I, III, V provide high tensile strength along collagen fibrils but toughness of the collagen scaffold as a whole depends on molecular bonds between distinct fibrils. Apart of other macromolecules in the extracellular matrix (ECM), collagen-specific interlinks involve microfilaments of collagen type VI, meshwork-organized collagen type VIII, and FACIT collagen type XIV. Basement membrane collagen types IV, XV, XVIII and cell-associated collagen XIII enable transmission of mechanical signals between cells and whole artery matrix. Collagen scaffold undergoes continuous remodeling by decomposition promoted with MMPs and reconstitution from newly produced collagen molecules. Pulsatile stress-strain load modulates both collagen synthesis and MMP-dependent collagen degradation. In this way the ECM structure becomes adoptive to mechanical challenges. The mechanoelastic properties of the arterial wall are changed in atherosclerosis concomitantly with collagen turnover both type-specific and dependent on the structure. Improving the feedback could be another approach to restore sufficient blood circulation.

Proteome Analysis of Human Arterial Tissue Discloses Associations Between the Vascular Content of Small Leucine-Rich Repeat Proteoglycans and Pulse Wave Velocity

“…In contrast to the observed regulation of the collagen fibrilassociated proteoglycans, none of the abundant fibrillar collagens (I, III, and V), 22 which all were present in our data set, were regulated.…”

“…Furthermore, it is also of interest that the SLRPs may also regulate collagen turnover because several SLRPs bind and regulate the strong inducer of matrix formation, transforming growth factor-β, hereby possessing antifibrotic properties. 20,21 In contrast to the observed regulation of the collagen fibrilassociated proteoglycans, none of the abundant fibrillar collagens (I, III, and V), 22 which all were present in our data set, were regulated.…”

“…[27][28][29] Collagen α-1 (IV) is abundantly present in the vascular wall, where it is the main component of basement membranes. 22 Its role in the vasculature is not well defined; however, it is interesting that a genome-wide association study of 4221 individuals found that a polymorphism in COL4A1 was highly significantly associated with PWV 30 and that an experimental study has found that mice with COL4A1 missense mutations display defects in several vascular functions and show low blood pressure. 31 It is moreover noteworthy that the arterial levels of these proteins are predictors of PWV, also when adjusting for blood pressure.…”

Direct visualization of the arterial wall water permeability barrier using CARS microscopy

“…These data are consistent with digitonin-soluble lipids playing a major role in the hydro-seal and with the IEL weakly contributing to the overall hydraulic resistance. Given the hydrophilic protein structure of the basement membrane (24,25), it is reasonable to conclude that the EBM is the major hydro-seal of the arterial wall.…”

Progenitor Cells, Bone Marrow–Derived Fibrocytes and Endothelial-to-Mesenchymal Transition

“…2 Healthy arteries are surrounded by perivascular adventitial tissue comprising collagens I and III in the intima, media, and adventitia, with collagen types I, III, IV, and V in the endothelial and vascular smooth muscle cell basement membranes. 3 These fibrillar proteins maintain vascular integrity and normal vascular tone and function. In hypertension, accumulation of collagen and fibronectin and ECM reorganization lead to increased stiffness of the vessel wall.…”