The Effect of Immunosuppressive Drugs on MMPs Activity in The Walls of Blood Vessels - A Systematic Review

Abstract

The current study focuses on the role of MMPs in the pathogenesis of the vascular damage and at the same time it offers the review referring to the influence of the immunosuppressive treatment on this interdependence. Contemporary immunosuppressive treatment constitutes of four groups of medications, such as: calcineurin inhibitors including cyclosporine A and tacrolimus; inhibitors of the inosine monophosphate dehydrogenase - the only agent from this group currently used in transplantation is mycophenalate mofetil (MMF); mTOR inhibitors, consisting of everolimus and glucocorticosteroids. Due to the fact that the properties of immunosuppressive drugs still remain unclear and transplant recipients need to use these medicines every day, knowledge of this should be further expanded. The deceases of the patients with the functioning graft who were diagnosed with the cardiovascular system diseases, constitute 50% of all renal transplant recipients. Immunosuppressive treatment leads to many pathological alterations within the organs and tissues and additionally they undoubtedly affect the activity of MMPs in the wall of the vessels.

Etiology, risk factors and management of hypertension post liver transplantation

“…Volume overload, inflammation in the context of allograft rejection, use of immunosuppressants and poor therapy compliance are the post‐transplant factors that contribute to the development of hypertension in liver transplant recipients 40 . Corticosteroids and calcineurin inhibitors cyclosporine A and tacrolimus are the immunosuppressants with a known blood pressure increasing effect 6–29 . Since calcineurin inhibitors are used as first‐line immunosuppressants, 1,2,7–11,41–43 the next section will focus on the mechanisms by which they cause hypertension.…”

“…Hypertension is a well‐known side effect of tacrolimus 6–29,37,38 . The physiological pathways involved in tacrolimus‐induced hypertension are summarized in Table 1.…”

“…The reported incidence of hypertension in pediatric liver transplant patients varies from 10% to 60%, depending on the methods and definitions used 6–29,37,38 . In a single‐center study by Lund et al 39 .…”

“…Since the procedure has favorable outcomes in both the short and long term, the focus has shifted towards the prevention and treatment of long‐term complications which are often related to the chronic use of immunosuppressive drugs 1–4,6 . Hypertension is a frequently occurring adverse effect of immunosuppression, in the first instance of calcineurin inhibitor tacrolimus, the cornerstone of most immunosuppressive protocols after liver transplantation 6–29 . It is a recognized risk factor for post‐transplant morbidity and mortality 11,22,24–27,29,30 .…”

The Effect of Calcineurin Inhibitors on MMPs Activity in Heart and Their Side Effects—A Review of Literature

“…The expression and activation of metalloproteinases is regulated by gene transcription, secretion of inactive forms of the enzyme by cells, and zymogen activation itself. Full activation is achieved by exposing the active site [ 27 , 28 ].…”