Cell-Cell Junctions and Extracellular Matrix Lecture Notes

Classification and molecular components of the aortic wall, the role of the extracellular matrix (ECM), and the pathogenesis of Abdominal Aortic Aneurysm (AAA).

Tunica intima

The inner layer of the aortic wall containing endothelial cells and an extracellular matrix network of laminin, collagen type IV, fibronectin, perlecan, and heparan sulfate.

Tunica media

The middle layer of the aortic wall consisting of smooth muscle cells, proteoglycans, glycoproteins, glycosaminoglycans, collagen, and elastin, responsible for compliance and recoil.

Tunica adventitia

The external layer of the aortic wall containing fibroblasts, collagen type I and III, and elastic fibers, providing tensile strength.

Internal elastic lamina

The structure that separates the tunica intima from the tunica media in the human aorta.

External elastic lamina

The structure that separates the tunica media from the tunica adventitia in the human aorta.

Basal lamina

A type of basement membrane with a mesh-like structure composed of non-fibrillar collagen, laminins, and fibronectin, upon which endothelial cells rest.

Elastin

A protein formed by the polymerization of tropoelastin monomers that allows for expansion and affects the flexibility of blood vessels.

Lamellar unit

A structural unit where elastin fibers are peripherally bound with smooth muscle cells and collagen fibers, coinciding with tension in the aortic wall.

Collagen type I

A fibril-forming collagen that provides resistance to the mechanical properties of the aorta's wall.

Collagen type III

A collagen that forms copolymers with collagen type I; its fraction determines the higher elasticity of the aorta's wall.

BMP1 and ADAMTS2

Metalloproteinases dependent on zinc and calcium ions that convert procollagens to self-assembling collagen monomers by removing $C-$ and $N-$ pro-peptides.

Matrix Metalloproteinases (MMPs)

A family of zinc-dependent endoproteinases that degrade the extracellular matrix and are involve in angiogenesis, cell apoptosis, and tissue repair.

Tissue Inhibitors of Metalloproteinases (TIMPs)

A group of four proteins (TIMP-1, -2, -3, and -4) that regulate MMP activity by binding covalently to prevent substrate access to the catalytic site.

Abdominal Aortic Aneurysm (AAA)

A multistage pathological process involving ECM degradation, inflammation, and abnormal remodeling of the vessel wall, potentially leading to rupture.

Osteogenesis imperfecta type XIII

A progressively deforming type 3 genetic disease caused by a mutation in the gene encoding BMP1.

Vascular Ehlers–Danlos Syndrome

A genetic disease manifested by the development of aneurysms caused by mutations in $COL3A1$.

Endothelial Cells (ECs)

The major cellular components of the tunica intima responsible for synthesizing inflammatory mediators, hormones, and factors like $NO$ and $PGI_2$.

Smooth Muscle Cells (SMCs)

Cells specific to the tunica media responsible for producing elastin and collagens that build the ECM in that part of the aorta.

Fibroblasts (FBs)

Cells specific to the tunica adventitia responsible for producing collagens, osteopontin, and fibronectin.