Table 3 Summary of network regulators, including findings from the present study, previously known biological links, effect directions, if druggable or status as a target of an available compound
From: Circulating causal protein networks linked to future risk of myocardial infarction
Regulator | Evidence from MR/Colocalization in AGES, and prior known biology related to ACVD* | Effect direction on ACVD and/or survival (Supplementary Data 15) | Druggable / available compound (Supplementary Data 16) |
|---|---|---|---|
ITIH3 | Gain-of-function variant increases risk of MI. Highly expressed in atherosclerotic lesion | Risk | Druggable |
HSPA1B | Causally linked to T2D and microvascular complications | Risk | Available compound |
DDX39B | Causally related to T2D and MetS (AGES) | Risk | Not druggable |
HSPA1A | Causally related to MetS (AGES). Causally linked to T2D and microvascular complications | Risk | Available compound |
KEAP1 | Cardiomyocyte-specific knockout mice show improved cardiac function | Protective | Available compound |
C2 | Deficiency increases atherosclerosis | Risk | Druggable |
PCDH8 | None | Risk | Not druggable |
GABARAP | Genetic links to hypertension and CVD | Risk | Not druggable |
CSH1/CSH2 | None | Protective | Druggable |
RFC4 | Genetic links to diabetes and venous thromboembolism | Risk | Not druggable |
IZUMO1 | None | Risk | Not druggable |
CSF3 | Promotes cardiomyocyte survival after MI | Risk | Druggable |
FABP3 | Contributes to ischemic heart injury | Risk | Not druggable |
KLKB1 | Causally protective against calcific aortic valve disease; influences cholesterol efflux | Protective | Available compound |
DCTN2 | None | Risk | Not druggable |
AFM | Positively associated with the metabolic syndrome, but lower levels in MI patients | Protective | Druggable |
AIPL1 | None | Protective | Not druggable |
MRRF | None | Protective | Not druggable |
APOA5 | Causally protective against MI and MetS (AGES). Knockout leads to elevated plasma triglycerides | Protective | Druggable |
PTPN11 | Gain-of-function mutations cause heart defects in oonan syndrome | Risk | Available compound |
CFB | Knock-out mice show improved metabolic and cardiovascular features | Risk | Available compound |
GAL3ST1 | None | Risk | Not druggable |
NUDT21 | None | Risk | Not druggable |
COL28A1 | Positively associated with HF and its subtypes | Risk | Druggable |
C11orf49 | Causally linked to MI (AGES) | Protective | Not druggable |
LRP4 | Causally linked to MI (AGES) | Inconclusive | Not druggable |
