We appreciate the interest of Dr Demopoulos and colleagues in our recent review on the association between COVID-19 and atherogenesis.1 We are thankful for the opportunity to elaborate further on the possible role of platelet-activating factor (PAF) in atherosclerosis and inflammation in COVID-19.
PAF is a potent pro-inflammatory phospholipid mediator known for its involvement in inflammation, immune response, atherosclerosis, and thrombosis.2 PAF acts through the activation of the PAF receptor, expressed in various cell types, including monocytes, macrophages, platelets, and endothelial cells,3 particularly in the presence of inflammation. PAF stimulates the expression of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1, which facilitate monocyte adhesion and infiltration into the endothelium, an early step in atherosclerosis.4 PAF also enhances the oxidative modification of low-density lipoprotein, facilitating its uptake by monocytes and foam cell formation, contributing to the progression of atherosclerosis and plaque instability.5
While the role of PAF in atherosclerosis is well reported, its specific involvement in COVID-19 pathophysiology is less understood. Antonopoulou et al6 suggested that the spike protein of SARS-CoV-2 may stimulate the release of PAF from monocytes and can contribute to the dysregulated immune response with elevated pro-inflammatory cytokines seen in COVID-19 patients. By amplifying the inflammatory response, increasing the recruitment of immune cells to the endothelium, and worsening oxidative stress, PAF could contribute to vascular damage in COVID-19 patients, thereby accelerating atherogenesis. Furthermore, PAF interacts with other inflammatory mediators implicated in COVID-19, such as interleukin-6 and tumor necrosis factor-alpha, potentially creating a feedback loop that sustains chronic inflammation and endothelial damage.7
In conclusion, we acknowledge the evolving complexity of the interplay between inflammation, platelet activation, and atherosclerosis in COVID-19 and the emerging literature regarding the possibility of PAF’s involvement in COVID-19-related cardiovascular complications, an important area for future exploration.
Footnotes
The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the Author Center.
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