TY - JOUR
T1 - Increased fractalkine and vascular dysfunction in obesity and in type 2 diabetes. Effects of oral antidiabetic treatment
AU - Schinzari, Francesca
AU - Tesauro, Manfredi
AU - Campia, Umberto
AU - Cardillo, Carmine
N1 - Funding Information:
This work was supported by grants from the Fondazione Roma (NCDS-2013-00000308) and the Ministero della Salute (RF-2010-2313809) to C. Cardillo, who is also partially supported by Fondi d'Ateneo grants from the Universit? Cattolica del Sacro Cuore. The intervention study was supported by a Beginning Grant-in-Aid of the American Heart Association to Dr. Umberto Campia.
Funding Information:
This work was supported by grants from the Fondazione Roma ( NCDS-2013-00000308 ) and the Ministero della Salute ( RF-2010-2313809 ) to C. Cardillo, who is also partially supported by Fondi d'Ateneo grants from the Università Cattolica del Sacro Cuore . The intervention study was supported by a Beginning Grant-in-Aid of the American Heart Association to Dr. Umberto Campia.
Publisher Copyright:
© 2020 Elsevier Inc.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/5/1
Y1 - 2020/5/1
N2 - Activation of fractalkine and other chemokines plays an important role in atherogenesis and, in conjunction with endothelial dysfunction, promotes premature vascular damage in obesity and diabetes. We hypothesized that increased circulating fractalkine coexists with impaired vasomotor function in metabolically healthy or unhealthy obesity, and that treatment with antidiabetic drugs may impact these abnormalities in type 2 diabetes. Compared to lean subjects, in both obese groups the vasodilator responses to acetylcholine and sodium nitroprusside were impaired (both P <.001); ETA-receptor blockade resulted in greater vasodilation (both P <.001); and plasma levels of fractalkine, E-selectin and monocyte chemoattractant protein (MCP)-1 were increased (all P <.05). In diabetic patients, oral antidiabetic drugs (glyburide, metformin or pioglitazone) reduced circulating levels fractalkine and E-selectin (both P <.05), without affecting vascular responses (all P >.05). Our findings indicate that insulin resistant states are associated with elevated atherogenic chemokines and impaired vascular reactivity. Antidiabetic treatment results in lower circulating fractalkine, which may provide cardiovascular benefits.
AB - Activation of fractalkine and other chemokines plays an important role in atherogenesis and, in conjunction with endothelial dysfunction, promotes premature vascular damage in obesity and diabetes. We hypothesized that increased circulating fractalkine coexists with impaired vasomotor function in metabolically healthy or unhealthy obesity, and that treatment with antidiabetic drugs may impact these abnormalities in type 2 diabetes. Compared to lean subjects, in both obese groups the vasodilator responses to acetylcholine and sodium nitroprusside were impaired (both P <.001); ETA-receptor blockade resulted in greater vasodilation (both P <.001); and plasma levels of fractalkine, E-selectin and monocyte chemoattractant protein (MCP)-1 were increased (all P <.05). In diabetic patients, oral antidiabetic drugs (glyburide, metformin or pioglitazone) reduced circulating levels fractalkine and E-selectin (both P <.05), without affecting vascular responses (all P >.05). Our findings indicate that insulin resistant states are associated with elevated atherogenic chemokines and impaired vascular reactivity. Antidiabetic treatment results in lower circulating fractalkine, which may provide cardiovascular benefits.
KW - Chemokines
KW - Diabetes
KW - Endothelium
KW - Fractalkine
KW - Obesity
UR - http://www.scopus.com/inward/record.url?scp=85082814566&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85082814566&partnerID=8YFLogxK
U2 - 10.1016/j.vph.2020.106676
DO - 10.1016/j.vph.2020.106676
M3 - Article
C2 - 32224233
AN - SCOPUS:85082814566
VL - 128-129
JO - Vascular Pharmacology
JF - Vascular Pharmacology
SN - 1537-1891
M1 - 106676
ER -