More detailed studies are required to decipher the role of PN-1 in cardiac fibrosis. Indeed, in pathological conditions, such as pressure overload models or myocardial infarction, inflammation plays an important role in adaptative and inadaptive responses, where monocytes and macrophages are key components of the inflammatory pathophysiology Because PN-1 is expressed by inflammatory cells and has been shown to be closely related to the inflammatory reaction in lung fibrosis, we can hypothesize that PN-1 can also participate in cardiac inflammation and consequently, in cardiac fibrosis.
The close relationships between PN-1 and proteases of the coagulation and fibrinolytic systems, as well as between PN-1 and the endocytic receptor LRP1, explain the impact of this serpin in the cardiovascular system Table 1. Essentially, PN-1 participates in maintaining the homeostatic function of the arterial wall and the cardiac tissue, as illustrated by its overexpression in the different cardiovascular pathologies mentioned in this review Figure 1.
Expected effect of PN-1 in cardiovascular diseases depending on its targets or partners. PN-1 in cardiovascular disease. Previous studies have shown PN-1 to be an important protective actor in atherosclerosis and TAA by reducing the impact of the proteolytic environment on the vascular cells. PN-1 is also involved in cardiac fibrosis but can be either anti-fibrotic and protective or pro-fibrotic and deleterious depending on its targets see Table 1.
CM and BR generated the figure and the table. VA and M-CB provided critical feedback and edited the review. All authors contributed to the review. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. National Center for Biotechnology Information , U. Journal List Front Cardiovasc Med v. Front Cardiovasc Med. Published online Mar Author information Article notes Copyright and License information Disclaimer.
This article was submitted to Atherosclerosis and Vascular Medicine, a section of the journal Frontiers in Cardiovascular Medicine. Received Jan 13; Accepted Mar The use, distribution or reproduction in other forums is permitted, provided the original author s and the copyright owner s are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
This article has been cited by other articles in PMC. Abstract The balance between proteases and protease inhibitors plays a critical role in tissue remodeling during cardiovascular diseases.
Keywords: PN-1, atherosclerosis, aneurysm, fibrosis, serpinE2, heart failure, smooth muscle cell. Biochemical Properties of PN-1 PN-1 inhibits a broad range of serine proteases explaining its physiological role in various processes ranging from coagulation and fibrinolysis to tissue remodeling and inflammation.
PN-1 in the Vascular System PN-1 does not circulate in plasma, but is present in blood cells, including platelets 13 , 14 and monocytes PN-1 in Vascular Diseases PN-1 and Atherosclerosis Atherosclerosis is a disease characterized by the thickening of the blood vessel wall due to the formation of plaques in the subendothelial intimal space.
PN-1 and Aneurysms Aortic aneurysms are also diseases characterized by intense remodeling due to an imbalance in favor of proteolytic degradation of the vascular wall ECM, leading to progressive dilation and eventually to rupture. PN-1 in Cardiac Fibrosis Myocardial fibrosis is an important pathophysiological process defined as an excessive accumulation of matrix proteins and is a well-established morbi-mortality marker.
Conclusions The close relationships between PN-1 and proteases of the coagulation and fibrinolytic systems, as well as between PN-1 and the endocytic receptor LRP1, explain the impact of this serpin in the cardiovascular system Table 1. Table 1 Expected effect of PN-1 in cardiovascular diseases depending on its targets or partners. Open in a separate window. Figure 1. Conflict of Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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