Axis Chemicals, Gene, or Molecule Targets CVD
CaMKII/Nav1.5 axis (7) Ca2+/calmodulin-dependent kinase II (CaMKII), PP2A-B56α PP2A regulates Nav1.5 activity in cardiomyocytes, B56α as a novel target Congenital and acquired human arrhythmia
Cardiosplenic axis (8) Proinflammatory leukocytes Splenic activation after ACS, leukocyte proinflammatory remodeling Acute coronary syndrome (ACS)
Cardiosplenic axis (9) Mononuclear phagocytes, antigen processing in the spleen Splenocytes immune-mediated injurious responses & the spleen to cardiac remodeling chronic heart failure (CHF)
CXCL1-CXCR2 axis (10)
Angiotensin II-induced infiltration of monocytes CXCL1-CXCR2 signalling
Inhibition of CXCL1 and/or CXCR2 & cardiac remodeling
Hypertensive heart diseases (cardiac remodeling)
CXCL12/CXCR4 chemokine ligand/receptor axis (11) Arterial CXCR4 (atheroprotective role) Arterial integrity, endothelial barrier function, and a normal contractile SMC phenotype Atherosclerosis
CXCR4/SDF-1 axis (12) The thrombin inhibitor bivalirudin did not interfere with BMC homing or SDF-1/CXCR4 signaling Bivalirudin but not heparin recommended as an anticoagulant for intracoronary infusion of BMCs for cell therapy Acute or chronic myocardial ischemia
KLF10-IL-9 signaling axis (13)
Ang II (angiotensin II) promoting CD4+ T-cell activation via upregulation of interleukins (IL)-9
Kruppel like factor 10 (KLF10 or Klf10) or IL-9 in T cells (novel therapeutic targets)
Perivascular Fibrosis & vascular disease
Leucopoietic-arterial axis (14) Higher air pollution exposure & socioeconomics, traffic noise, and risk factors Higher leucopoietic tissue activity and arterial inflammation (ArtI) CVD & major adverse cardiovascular events (MACE)
Lipoprotein(a)-lipoprotein-associated phospholipase A2-oxidized phospholipid axis (Lp-PLA2 axis) (15) Ysophosphatidylcholine Valve interstitial cells Calcific aortic valve stenosis (CAVS), acquired valvular heart disease
miR-208-Mef2 axis (Mef2-microRNAs axis) (16)
Myocyte enhancer factor 2 (Mef2)
Mef2 regulates microRNAs for cardiac development and disease
Pulmonary hypertension & Right ventricular failure
miR-223/PDGFRβ VSMC Axis (17)
Platelet miR-223 or VSMC PDGFRβ
Lack of miR-223 & VSMC dedifferentiation and medial damage
Coronary artery pathology in Kawasaki Disease (acute vasculitis of early childhood)
NFATc3/miR-204 axis (18)
Macrophage NFATc3, a negative regulator of atherogenesis
Up-regulation of NFATc3 in macrophages, up-regulates miR-204 to reduce SR-A and CD36 levels
Atherosclerosis (preventing foam cell formation)
Nuclear Ca2+-CaMKIIδC axis (19)
CaMKII (Ca2+-Calmodulin dependent protein kinase) δC
Early transaortic constriction perinuclear CaMKIIδC activation, myocyte Ca2+ transients and nuclear transcriptional responses
Eccentric hypertrophy and heart failure (HF)
p38α-CREB-OGDH axis (20) Plasma succinate concentrations Macrophages Aortic aneurysm and dissection (AAD)
p-Erk1/2-MMP axis (21)
Lower serum uric acid (SUA) levels
Smooth muscle cell (SMC)-elastin contractile units (degradation of elastin)
Recurrent intracerebral hemorrhage (R-ICH)
Sirt1/p53/p21 axis (22) Metoprolol Arginine vasopressin (AVP)-Induced Cellular Senescence in H9C2 Cardiomyocytes & the AVP-induced expression of acetylated p53 and p21 Ischemia injury in cardiovascular system
SR-A1-c-Myc axis (23) Tissue-resident and monocyte-derived cardiac macrophage Endothelial progenitor cells differentiation & neovascularization Doxorubicin-Induced Cardiomyopathy (DiCM)
Vegfc-Emilin2a-Cxcl8a Signaling axis (24) Vegfc, emilin2a and cxcl8a  for coronary revascularization & Cardiac Regeneration Coronary endothelial cells upregulate vegfc, vegfc signaling upregulates epicardial emilin2a and cxcl8a expression Ischemic heart disease