Pulmonary vascular remodeling occurs in severe equine asthma

PURPOSE OF THE STUDY (max 480 characters): Severe equine asthma is characterized by airway obstruction due to neutrophilic inflammation, lung remodeling, and hypoxemia. Chronic hypoxemia triggers persistent pulmonary vasoconstriction that may induce muscular artery remodeling resulting in increased vascular resistance and pulmonary hypertension (PH), as end-stage disease. We investigated pulmonary artery remodeling in severe equine asthma, as, to the best of our knowledge, this has not been yet studied and may represent a therapeutic target for preventing PH onset. METHODS USE (max 720 characters): Lung biopsy specimens were collected via thoracoscopy from 6 asthmatic and 5 age-matched control horses. Histomorphometric assessment was performed on Movat-Russell stained histological sections, evaluating pulmonary artery wall area, intimal area, medial area and how they were correlated (Pearson coefficient) with the artery size, expressed as internal elastic lamina length. The total amount of smooth muscle within the artery wall and the density of proliferating smooth muscle cells were similarly estimated using immunostaining for α-smooth muscle actin (α-SMA) and proliferating cell-associated nuclear antigen (PCNA). Values were compared using a one-tailed t Student test with Welch’s correction (p < 0.05). SUMMARY OF RESULTS (max 720 characters): The pulmonary artery wall area and the total amount of smooth muscle within the artery wall were significantly increased in asthmatic horses when compared to controls. Furthermore, intimal area and internal elastic lamina length was correlated in control horses, but not in asthmatic horses. The pulmonary artery medial and intimal area, the density of proliferating smooth muscle cells and the correlation between medial area and internal elastic lamina length did not differ between the two groups. CONCLUSIONS (max 960 characters): Pulmonary artery remodeling associated with smooth muscle hypertrophy and intimal muscolarization occurs in severe equine asthma, resulting in overall pulmonary artery lumen reduction that persists during clinical remission of the disease. Artery smooth muscle hypertrophy and intimal muscolarization may be induced by recurrence of hypoxic vasoconstriction stimulus and release of cytokines from inflammatory cells infiltrating the annexed airways. Persistent artery lumen reduction increases overall vascular resistance and smooth muscle hypertrophy enhances vasoconstriction effects, and this could lead to the onset of PH and eventually to PH-associated cardiovascular complications.