Microvascular Leakage as Therapeutic Target for Ischemia and Reperfusion Injury

Abstract

Reperfusion injury is a very common complication of various indicated therapies such as the re-opening of vessels in the myocardium or brain as well as reflow in hemodynamic shutdown (cardiac arrest, severe trauma, aortic cross-clamping). The treatment and prevention of reperfusion injury has therefore been a topic of immense interest in terms of mechanistic understanding, the exploration of interventions in animal models and in the clinical setting in major prospective studies. While a wealth of encouraging results has been obtained in the lab, the translation into clinical success has met with mixed outcomes at best. Considering the still very high medical need, progress continues to be urgently needed. Multi-target approaches rationally linking interference with pathophysiological pathways as well as a renewed focus on aspects of microvascular dysfunction, especially on the role of microvascular leakage, are likely to provide new insights.

Mesenchymal stromal cells secretome restores bioenergetic and redox homeostasis in human proximal tubule cells after ischemic injury

“…For instance, T-cells, particularly CD3 + T-cells, have been shown to play a significant role in mediating post-ischemic damage by increasing the release of pro-inflammatory cytokines [ 79 ], whereas regulatory T-cells have an anti-inflammatory role in IRI [ 80 ]. Furthermore, microvascular leakage is another hallmark of IRI, exacerbating ischemic damage by inducing, among others, the release of inflammatory cytokines by leukocytes (e.g., lymphocytes) [ 81 , 82 ]. To address this, integrating models like organ-on-chip systems would provide a more accurate representation of the complex cellular interplay between the various cell types.…”