Letter to the Editor Regarding “Cardiovascular Insights for the Appropriate Management of Chronic Venous Disease: A Narrative Review of Implications for the Use of Venoactive Drugs”

Dear Editors,

We read with huge interest the review “Cardiovascular insights for the appropriate management of chronic venous disease: a narrative review of implications for the use of venoactive drugs” [1]. We congratulate the authors for the broad overview presented and for the broadness of the information. After all, pharmacological actions on a complex system such as the human one represent not the arithmetic sum of the individual situations that arise but something different, linked to the interactions of the system itself between the various apparatuses and organs, aimed at responding to the new state of homeostasis, characteristic of each individual.

Specifically, we would like to contribute by suggesting some food for thought on the probable main mechanism of the action of diosmin towards an important endothelial cell structure, namely the endothelial glycocalyx [2], with impact on the subsequent actions described in the review.

Based on the well-known mechanism of this molecule on norepinephrine reabsorption [3], we hypothesise that the action takes place by inducing a reduction in the capillary bed, resulting in less fluid filtration in the interstitium and more lymphangia contractions [4]. This results in faster drainage of interstitial oedema, caused by the ongoing inflammatory state and metabolic distress of the cells. This reduction in oedema brings improved oxygenation and nutrition to the cells and more efficient removal of catabolites. These improved conditions at the cellular level bring the cell the possibility of repairing its own glycocalyx with restoration of the physiological electrochemical gradient and consequent electronegativity linked to sialic acid. In this way, therefore, it is possible to explain mechanistically the various beneficial effects of diosmin, which can be summarised as: (1) improvement of cell membrane fluidity; (2) reduction of capillary hyperpermeability; (3) restoration of physiological conditions of rolling, adhesion and leucocyte migration; (4) reduction of thrombus formation at the venous level.

We intend to draw researchers' attention to these aspects to extend and improve this thought-provoking review.

Author Contribution

Mauro Poggialini: concept and design, drafting the manuscript. Valter Travagli: concept and design, writing and revising the manuscript, gathered references. Both the authors approved the final version.

Funding

No funding or sponsorship was received for this study or publication of this article.

Data Availability

Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.

Declarations

Conflict of Interest

Mauro Poggialini and Valter Travagli have nothing to disclose.

Ethical Approval

This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors.