Dr Giuseppina Caligiuri is an expert in molecular mechanisms underlying the interplay between inflammation and vascular biology.
She has been particularly focused on the regulatory functions of CD31, the most abundant endothelial surface glycoprotein endowed with critical co-signaling properties in cardiovascular physiology and pathology (Caligiuri G.Mechanotransduction, immunoregulation, and metabolic functions of CD31 in cardiovascular pathophysiology. Cardiovasc Res. 2019 Jul 1;115(9):1425-1434. Caligiuri G. CD31 as a Therapeutic Target in Atherosclerosis. Circ Res. 2020 Apr 24;126(9):1178-1189).
Regulation of endothelial function face to a systemic inflammatory process is crucial for the clinical outcome of pulmonary and systemic circulation. In the case of sepsis, the eradication of the pathogen may be useless because the uncontrolled release of vasoactive mediators acting on the hemodynamics (vasoplegia, peripheral hypoperfusion) as well as of factors affecting the endothelial barrier and anti-coagulant functions of organ microvessels in response to pathogens (oedema and disseminated intravascular coagulation) eventually lead leading to multi-organ failure and fatal outcome.
Intriguingly, the loss of CD31 favours the occurrence of oedema and disseminated intravascular coagulation and aggravates the outcome of septic choc, in mice (Luo L et al. PECAM-1 protects against DIC by dampening inflammatory responses via inhibiting macrophage pyroptosis and restoring vascular barrier integrity. Transl Res. 2020;222:1-16), suggesting that the massive cytokine release and inappropriate intravascular activation of homeostasis observed in patients affected by the most severe forms of COVID-19 may in part be due to a defective control of immune effectors within the circulation.
While waiting for an effective vaccine, multiple endothelial/inflammatory mechanisms and potential therapeutic solutions, including the use of anti-cytokine biologicals (Xu X et al. Effective treatment of severe COVID-19 patients with tocilizumab. Proc Natl Acad Sci U S A. 2020;117:10970-10975), can be envisaged to prevent cardiovascular fatal complications in patients with Covid-19.