Therapeutic Targeting of the Proinflammatory IL-6-JAK/STAT Signalling Pathways Responsible for Vascular Restenosis in Type 2 Diabetes Mellitus

Table 1

Selected IL-6–JAK/STAT–SOCS3 modulators and their impact on cardiovascular disease.

Agent	Mode of action	Type of study	Outcome
Sirukumab	IL-6-blocking antibody	In vitro	↓ Adhesion molecule expression; ↑ SMC contractile phenotype
Fc-sgp130	IL-6 trans-signalling inhibitor	In clinic	Awaiting outcome
Tocilizumab	IL-6Rα-blocking antibody to inhibit classical and trans-signalling	In vitro; In clinic	↓ Adhesion molecule expression; ↑ SMC contractile phenotype; Approved for rheumatoid arthritis and systemic juvenile idiopathic arthritis; ↑ IP-10 and MIP-1β in acute phase STEMI
Tofacitinib	JAK inhibitor	In clinic	Approved for rheumatoid arthritis; No effect on cardiovascular risk
Ruxolitinib	JAK inhibitor	In clinic	Approved for polycythemia vera and myelofibrosis no studies reporting on cardiovascular system
OBP-31121	STAT3 inhibitor	Clinical trial	↑ Peripheral neuropathy no studies reporting on the cardiovascular system
Adenoviral SOCS3	Increases SOCS3-mediated inhibition of signalling	In vivo	↓ SMC inflammation, migration, and proliferation; ↓ NIH

Selected existing therapies targeting the IL-6–JAK/STAT–SOCS3 signalling pathway. Please see text for detail and references.