|Smooth muscle hyperplasia|
Thursday, February 12, 2015
Canadian HealthCare: Smooth muscle hyperplasia
Imatinib is a tyrosine kinase inhibitor used for the treatment of chronic myeloid leukemia by inhibiting BCR-ABL kinase activity. It can also block other factors, such as c-kit ligand, stem cell factor, and platelet-derived growth factor (PDGF) receptor tyrosine kinase activity. It was reported to block the increase of ASM mass in a mouse asthma model.
PDGF receptor is a receptor tyrosine kinase. Its signaling, known as a cell migration inducer, also causes ASMC proliferation. Hirota et al showed its plausibility as an agent of remodeling by demonstrating an increase of ASM mass and cellular proliferation using an adenovirus-mediated PDGF overexpression mouse asthma model.
TGF-b is a pleiotropic cytokine, which was reported to increase in the asthmatic airways. Its expression can be detected in both immune cells and structural cells. In a COPD mouse model, Podowski et al showed the improvement of subepithelial collagen deposition and airway wall thickening by inhibition of TGF-b.
Eotaxin (CCL) is a chemokine that is known for its potent chemoattractant effect for eosinophils. Using a mouse model, Wegmann et al reported that antagonizing CCR, an eotaxin receptor, prevented some features of airway remodeling, goblet metaplasia, subepithelial fibrosis, and increase of number of myofibroblasts.
Based on the pathologic findings, the cellular events occurring in airway remodeling are smooth muscle hyperplasia and hypertrophy, epithelial cell hyperplasia and goblet cell metaplasia, subepithelial fibrosis, and neovascularization. Smooth muscle hyperplasia is inferred by the increase of their proliferation and migration. Asthmatic ASMCs in culture retain the property of more rapid proliferation rates compared with normal ASMC. ASMC migration toward the airway epithelium has been suggested from the findings on proximal asthmatic airway bronchial biopsy samples. It is postulated that ASMC migration may be a contributor to the expansion of smooth muscle bundles.
Physiologic scales and symptoms have been used to assess the clinical states of patients with asthma. Given the fact that asthma and COPD are inflammatory syndromes and complexes of several phenotypes that cause reversible or partial airway narrowing, more detailed classification of the patients and appropriate therapies for each group are necessary. For example, treatment strategies based on monitoring sputum eosinophil counts reduce asthma exacerbations. However, we are lacking specific biomarkers that reflect airway remodeling.