The matrix metalloproteinase-10 (MMP-10) enzyme that’s produced by infiltrating macrophages contributes to vascular remodeling in pulmonary arterial hypertension (PAH), a new study published in the International Journal of Biological Sciences found.
This finding suggests that circulating MMP-10 could be used as a potential therapy for PAH, Pei-Ling Chi and the coauthors of the study said.
PAH is a rare and progressive type of pulmonary hypertension, which can be idiopathic, hereditary, induced by drugs or toxins, or associated with other diseases such as HIV infections, connective tissue disease, portal hypertension, congenital heart disease, or schistosomiasis.
Read more about PAH etiology
It is characterized by vascular remodeling, which involves vascular smooth muscle cell proliferation and excessive extracellular matrix modulation. It is known that the dysregulation of matrix metalloproteinases (MMPs), secreted enzymes that can digest the vascular matrix, can lead to vascular remodeling.
The present study has shown that the levels of matrix metalloproteinase-1 and MMP-10 are increased in the medial layer of the blood vessel walls as well as the serum and M1-polarized macrophages both in the lungs of rodent models of PAH and in patients with the disease.
“MMP-10 regulates the malignant phenotype of pulmonary artery smooth muscle cells,” the researchers wrote. They also showed that the overexpression of active MMP-10 upregulates cyclin D1 and proliferating cell nuclear antigen, thereby promoting pulmonary artery smooth muscle cell proliferation and migration.
Finally, they found that the inhibition of signal transducer and activator of transcription 1 (STAT1), which is known to be involved in regulating the expression of MMPs, inhibits the expression of hypoxia-induced MMP-10 in M1-polarized macrophages from patients with PAH.
“Our study presents a potential therapeutic strategy for PAH by using STAT1 as a target to regulate MMP-10 levels,” they concluded.
Chi PL, Cheng CC, Hung CC, et al. MMP-10 from M1 macrophages promotes pulmonary vascular remodeling and pulmonary arterial hypertension. Int J Biol Sci. 2022;1;18(1):331-348. doi:10.7150/ijbs.66472