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. 2024 Feb 24;25(5):2658. doi: 10.3390/ijms25052658

Table 1.

Biomarkers and potential treatments for CRS.

Clinical Marker Pathophysiological Significance Healthy Adult Plasma Range Relevant Pharmacological Agents (Clinical or Experimental) References
Asymmetric dimethyl arginine (ADMA) Reduces the following:
  • -

    NO bioavailability

  • -

    Oxygen delivery

  • -

    Cardiac blood flow and cardiac output

 0.4–1.0 µmol/L Antioxidants [148,153,154]
Estrogen
Vitamin A
ACEi
ARBs
HMG-CoA reductase inhibitors (statins)
Endothelin-1 (ET-1)
  • -

    Increases mean arterial blood pressure

  • -

    Promotes vasoconstriction and myocardial/vascular fibrosis + hypertrophy

  • -

    Increases cytokine + growth factor production

 0.1–5 pg/mL ET receptor antagonists (bosentan and ambrisentan)—not beneficial in HF [155,156,157]
SGLT2i
Syndecan 4 (SDC4) Part of the endothelial glycocalyx
  • -

    Regulates coagulation, cell adhesion, growth, and inflammation

 5.7–16.05 ng/mL Not tested in CV literature [158]
N-terminal prohormone of brain natriuretic peptide (NT-proBNP)
  • -

    Inhibits RAAS, ADH, and endothelin system

  • -

    Promotes renal afferent arteriolar dilatation and efferent arteriolar constriction

  • -

    Stimulates natriuresis

 <125 pg/mL Nesiritide (recombinant BNP)—not beneficial in HF [159,160,161]
Neprilysin—sacubitril (endopeptidase degrading ANP/BNP)—beneficial with ACEi or ARB
High-sensitivity C-reactive protein (hs-CRP)
  • -

    Pro-inflammatory + prothrombotic effects—promotes vascular dysfunction

  • -

    Activates RAAS

  • -

    Remodels atherosclerotic plaque

  • -

    Induces oxidative stress

 <3 mg/L No specific drugs target hs-CRP
Interluekin-6 (IL-6) Pro-inflammatory, stimulates the following:
  • -

    Endothelial activation

  • -

    Vascular smooth muscle cell proliferation

  • -

    Leukocyte recruitment and contributes to atherosclerotic plaque growth

 <5 pg/mL Anti-IL-6 antibody (ziltivekimab) [69,70,162,163]
Anti-IL-6R antibody (tocilizumab)
Statins
SGLT2i
Tumor necrosis factor alpha (TNF-α) Pro-inflammatory
  • -

    Alters vascular tone and increases microvascular permeability

 <6 pg/mL TNF-α inhibitors
  • -

    Etanercept, infliximab, adalimumab, certolizumab pegol, golimumab

 [110,163]
SGLT2i
Monocyte chemotactic protein-1 (MCP-1) (also known as CCR2)
  • -

    Promotes monocyte, macrophage, and Treg recruitment

  • -

    Facilitates angiogenesis, involved in tumour/cancer development, and is associated with autoimmune, metabolic, and cardiovascular diseases

 <150 pg/mL MCP-1 antagonist (propagermanium), anti-CCR2 antibody (MLN1202) [164,165]
Statins
PPARα activators (fenofibrate)
Most data are from pre-clinical studies
CD47 Cell-surface receptor
  • -

    Regulator of phagocytosis and “marker of self”

  • -

    Has roles in apoptosis, proliferation, adhesion, and migration

 not measured CD47 monoclonal antibody (magrolimab) [166,167]
Signal regulatory protein alpha (SIRP-α) Transmembrane protein, modulates leukocyte immune responses, e.g., adhesion, migration, and phagocytosis, CD47/SIRPα axis, “don’t eat me” signal not measured CD47-SIRPα/Fc fusion proteins
  • -

    All investigational

Abbreviations: ADH—antidiuretic hormone; ANP—atrial natriuretic peptide; ACEi—angiotensin-converting enzyme inhibitor; ARB—angiotensin receptor blocker; CCR2—C-C chemokine receptor 2; NO—nitric oxide; PPARαperoxisome proliferator activated receptor γ; RAAS—renin–angiotensin–aldosterone system; SGLT2i—sodium-glucose cotransporter 2 inhibitor; Treg—regulatory T lymphocytes.