title: Microvascular targets for anti-fibrotic therapeutics.
abstract: Fibrosis is characterized by excessive extracellular matrix deposition and is the pathological outcome of repetitive tissue injury in many disorders. The accumulation of matrix disrupts the structure and function of the native tissue and can affect multiple organs including the lungs, heart, liver, and skin. Unfortunately, current therapies against the deadliest and most common fibrosis are ineffective. The pathogenesis of fibrosis is the result of aberrant wound healing, therefore, the microvasculature plays an important role, contributing through regulation of leukocyte recruitment, inflammation, and angiogenesis. Further exacerbating the condition, microvascular endothelial cells and pericytes can transdifferentiate into matrix depositing myofibroblasts. The contribution of the microvasculature to fibrotic progression makes its cellular components and acellular products attractive therapeutic targets. In this review, we examine many of the cytokine, matrix, and cellular microvascular components involved in fibrosis and discuss their potential as targets for fibrotic therapies with a particular focus on developing nanotechnologies.
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, Connecticut.
authors.forename: Kai-Ming T
authors.initials: KM
authors.lastname: Pu
authors.affiliation: Department of Biomedical Engineering, Yale University, New Haven, Connecticut.
authors.forename: Parid
authors.initials: P
authors.lastname: Sava
authors.affiliation: Department of Biomedical Engineering, Yale University, New Haven, Connecticut.
authors.forename: Anjelica L
authors.initials: AL
authors.lastname: Gonzalez
mesh_terms: D016207:Cytokines / Q000037:antagonists & inhibitors / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods*; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D005355:Fibrosis; D006801:Humans; D055806:Microvessels / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008954:Models, Biological; D058990:Molecular Targeted Therapy / Q000379:methods; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D036103:Nanotechnology / Q000379:methods*
chemical_list: D016207:Cytokines
keywords: TGFβ; fibrocyte; fibrosis; microvasculature; nanomedicine; nanoparticle