TY - JOUR
T1 - Methotrexate and cardiovascular prevention
T2 - an appraisal of the current evidence
AU - Mangoni, Arduino A.
AU - Sotgia, Salvatore
AU - Zinellu, Angelo
AU - Carru, Ciriaco
AU - Pintus, Gianfranco
AU - Damiani, Giovanni
AU - Erre, Gian Luca
AU - Tommasi, Sara
PY - 2023/1/1
Y1 - 2023/1/1
N2 - New evidence continues to accumulate regarding a significant association between excessive inflammation and dysregulated immunity (local and systemic) and the risk of cardiovascular events in different patient cohorts. Whilst research has sought to identify novel atheroprotective therapies targeting inflammation and immunity, several marketed drugs for rheumatological conditions may serve a similar purpose. One such drug, methotrexate, has been used since 1948 for treating cancer and, more recently, for a wide range of dysimmune conditions. Over the last 30 years, epidemiological and experimental studies have shown that methotrexate is independently associated with a reduced risk of cardiovascular disease, particularly in rheumatological patients, and exerts several beneficial effects on vascular homeostasis and blood pressure control. This review article discusses the current challenges with managing cardiovascular risk and the new frontiers offered by drug discovery and drug repurposing targeting inflammation and immunity with a focus on methotrexate. Specifically, the article critically appraises the results of observational, cross-sectional and intervention studies investigating the effects of methotrexate on overall cardiovascular risk and individual risk factors. It also discusses the putative molecular mechanisms underpinning the atheroprotective effects of methotrexate and the practical advantages of using methotrexate in cardiovascular prevention, and highlights future research directions in this area.
AB - New evidence continues to accumulate regarding a significant association between excessive inflammation and dysregulated immunity (local and systemic) and the risk of cardiovascular events in different patient cohorts. Whilst research has sought to identify novel atheroprotective therapies targeting inflammation and immunity, several marketed drugs for rheumatological conditions may serve a similar purpose. One such drug, methotrexate, has been used since 1948 for treating cancer and, more recently, for a wide range of dysimmune conditions. Over the last 30 years, epidemiological and experimental studies have shown that methotrexate is independently associated with a reduced risk of cardiovascular disease, particularly in rheumatological patients, and exerts several beneficial effects on vascular homeostasis and blood pressure control. This review article discusses the current challenges with managing cardiovascular risk and the new frontiers offered by drug discovery and drug repurposing targeting inflammation and immunity with a focus on methotrexate. Specifically, the article critically appraises the results of observational, cross-sectional and intervention studies investigating the effects of methotrexate on overall cardiovascular risk and individual risk factors. It also discusses the putative molecular mechanisms underpinning the atheroprotective effects of methotrexate and the practical advantages of using methotrexate in cardiovascular prevention, and highlights future research directions in this area.
KW - atherosclerosis
KW - heart disease risk factors
KW - immunity
KW - inflammation
KW - methotrexate
UR - http://www.scopus.com/inward/record.url?scp=85180758475&partnerID=8YFLogxK
U2 - 10.1177/17539447231215213
DO - 10.1177/17539447231215213
M3 - Review article
C2 - 38115784
AN - SCOPUS:85180758475
SN - 1753-9455
VL - 17
SP - 1
EP - 22
JO - Therapeutic advances in cardiovascular disease
JF - Therapeutic advances in cardiovascular disease
ER -