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Polymorphonuclear leukocytes in ischemic vascular disease
1Department of Physiology & Biophysics, USC School of Medicine, Los Angeles.
Abstract:
Over the last decade, an extensive amount of evidence has accumulated which implicates PMN in the etiology and pathophysiology of ischemic/thrombotic diseases. It has become apparent that PMN infiltration is not, as once thought, an innocent secondary phenomenon following ischemia. Rather, PMN are active participants in the pathophysiology of infarction, exacerbating the tissue damage. Since the development of means to achieve reperfusion after thrombosis, this phenomenon has become of critical importance. Many different approaches, targeted at prevention of PMN trapping in the capillaries of the ischemic, area, have been shown to effectively reduce the final infarct size, and will likely prove valuable adjuncts to reperfusion. However, perhaps the most significant aspect of the realization that PMN play a significant role in thrombotic disease may prove to be the potential for early intervention: Elevated PMN counts are predictive of ischemic events, and there is preliminary evidence that the elevated PMN count may be also associated with increased PMN activation, suggesting that research directed at the prophylactic use of anti-PMN agents might someday prove effective in reducing the incidence of MI and stroke.
Insights
Polymorphonuclear neutrophils (PMN) actively contribute to tissue damage in ischemic diseases. Targeting PMN offers a promising strategy for reducing infarct size and preventing events like myocardial infarction (MI) and stroke.
Area of Science:
- Cardiovascular Research
- Immunology
- Pathophysiology
Background:
- Accumulating evidence implicates polymorphonuclear neutrophils (PMN) in the development and progression of ischemic/thrombotic diseases.
- PMN infiltration is now understood as an active contributor to infarction pathophysiology, rather than a passive consequence of ischemia.
- The role of PMN is critical in the context of reperfusion therapies for thrombosis.
Purpose of the Study:
- To review the established role of PMN in ischemic/thrombotic diseases.
- To highlight the therapeutic potential of targeting PMN in reducing tissue damage and infarct size.
- To explore the implications of PMN's role for early intervention and prophylactic strategies.
Main Methods:
- Review of accumulated scientific evidence and research findings.
- Analysis of the pathophysiology of PMN involvement in ischemic events.
- Evaluation of therapeutic approaches targeting PMN in preclinical and clinical studies.
Main Results:
- PMN are active participants exacerbating tissue damage in infarction.
- Interventions preventing PMN trapping in ischemic areas effectively reduce infarct size.
- Elevated PMN counts predict ischemic events and may indicate increased PMN activation.
Conclusions:
- PMN play a significant role in thrombotic diseases, contributing to pathophysiology and exacerbating damage.
- Targeting PMN offers a viable strategy to reduce infarct size and improve outcomes following reperfusion.
- Prophylactic strategies targeting PMN may hold potential for reducing the incidence of myocardial infarction and stroke.