elastin and Disease

Fibrillins (FBNs) are key relay molecules that form the backbone of microfibrils in elastic and non‑elastic tissues. Interacting with other components of the extracellular matrix (ECM), these ubiquitous glycoproteins exert pivotal roles in tissue development, homeostasis and repair. In addition to mechanical support, FBN networks also exhibit regulatory activities on growth factor signalling, ECM formation, cell behaviour and the immune response. Consequently, mutations affecting the structure, assembly and stability of FBN microfibrils have been associated with impaired biomechanical tissue properties, altered cell‑matrix interactions, uncontrolled growth factor or cytokine activation, and the development of fibrillinopathies and associated severe complications in multiple organs. Beyond a panoramic overview of structural cues of the FBN network, the present review will also describe the pathological implications of FBN disorders in the development of inflammatory and fibrotic conditions.

Topics: Animals; Disease; Elastin; Extracellular Matrix; Fibrillin-1; Humans; Intercellular Signaling Peptides and Proteins; Signal Transduction

Elastin is the protein responsible for the resilience of vertebrate tissue. It is an extremely stable protein deposited during the early stages of life and experiencing almost no renewal. As a consequence, it can be considered that each individual has an elastin capital for life. Despite its extreme stability, elastin can be degraded by several enzymes termed elastases. Elastases are among the most aggressive proteases, and their presence is increased with age. As a consequence, elastin fragmentation resulting in the generation of elastin peptides is one of the hallmarks of aging. This review will examine their nature and further expose our current understanding of the role played by these peptides in aging and their contribution to tissue homeostasis and several pathologies.

Topics: Aging; Animals; Disease; Elastin; Homeostasis; Humans; Peptides; Proteolysis

It is now well accepted that aging is associated with the occurrence of a low-grade inflammation called Inflamm-aging. This leads to the imbalance between the various mediators of the inflammatory response in favour of the pro-inflammatory response represented by pro-inflammatory cytokines and oxidative stress. The question that arises, and is still under investigation, what is the origin of the driving force leading to these changes. One of the current hypotheses is that chronic stimulation of the immune system contributes to the pro-inflammatory shift. The chronic stimulation can be of viral origin such as cytomegalovirus, from tumor antigens or from other sources such as the extracellular matrix, especially from elastin fibres and collagens. Aging and various inflammatory diseases such as atherosclerosis, abdominal aortic aneurysms, chronic obstructive pulmonary diseases (COPD), cancer and type 2 diabetes are characterized by the destruction of elastin fibers and the consequent generation of elastin peptides which are biologically active. This review will describe the putative contribution of elastin peptides to inflamm-aging and extend on their role on immunosenescence, as well as on age-associated chronic inflammatory diseases.

Topics: Adaptive Immunity; Aging; Animals; Disease; Elastin; Humans; Immunity, Innate; Inflammation; Models, Biological; Peptides

Topics: Amino Acids; Animals; Aorta; Cartilage; Collagen; Connective Tissue; Contractile Proteins; Culture Techniques; Disease; Elastic Tissue; Elastin; Extracellular Matrix Proteins; Fluorescent Antibody Technique; Glycoproteins; Humans; Ligaments; Lung; RNA Splicing Factors

Topics: Aorta; Aortic Diseases; Arteriosclerosis; Disease; Elastin; Humans; Proteins