Development of ApoA-I Modulators for Cardiovascular Diseases

In clinical practice, reduced levels of apolipoprotein A1 (ApoA-I) in serum or plasma are associated with an increased risk of cardiovascular and cerebrovascular diseases. Ace Therapeutics, a leading contract research organization, provides comprehensive outsourcing services for cardiovascular disease research and drug development, supporting the advancement of novel ApoA-I modulators to address unmet medical needs.

The Role of ApoA-I in Cardiovascular Diseases

ApoA-I is the primary structure of high-density lipoprotein (HDL), constituting approximately 70% of HDL protein content. ApoA-I plays a critical role in reverse cholesterol transport, facilitating the movement of cholesterol from peripheral tissues, including arterial walls, to the liver for metabolism and excretion. Additionally, ApoA-I exhibits anti-inflammatory, antioxidant, and vascular endothelial protective properties. By promoting reverse cholesterol transport, ApoA-I reduces cholesterol deposition in arterial walls, slowing the progression of atherosclerosis. Consequently, ApoA-I levels are positively correlated with HDL levels, and low levels of ApoA-I and HDL are independent risk factors for coronary heart disease.

Fig. 1 Generation and assembly of ApoA-I (Tao X, et al., 2024)

Discovery of ApoA-I Modulators

• ApoA-I Mimetic Peptides
  We provide next-generation ApoA-I mimetic peptide discovery services, developing analogs with enhanced stability and potent anti-atherogenic activity for the treatment of atherosclerosis and coronary artery disease.
• Small Molecule Drugs to Stimulate ApoA-I Expression
  Our drug discovery services support the identification and optimization of small-molecule drugs that upregulate ApoA-1 expression or stability.

In Vitro Pharmacodynamic Studies

• Cholesterol Efflux Assay for Reverse Cholesterol Transport
  Using cholesterol efflux fluorometric assay kits, we assess the capacity of drug candidates to facilitate cholesterol transport from macrophages to the liver.
• In Vitro Evaluation Using ApoA-I-Expressing Cell Lines
  We employ ApoA-I-expressing cell lines, including hepatocytes and macrophages, to evaluate the potency and efficacy of investigational compounds.

In Vivo Pharmacodynamic Studies

• Effects on Atherosclerosis
  We provide customized animal models of atherosclerosis, such as ApoE knockout mice and LDLR knockout mice, to evaluate the anti-atherosclerotic effects of drug candidates.
• Effects on Hypercholesterolemia
  We offer specialized animal models of hypercholesterolemia, such as high-fat diet-induced hypercholesterolemia models, to assess the lipid-lowering effects of drug candidates.
• Effects on Myocardial Infarction
  We develop customized myocardial infarction models, such as coronary artery ligation-induced models, to evaluate the cardioprotective effects of drug candidates.

Ace Therapeutics, with long-standing experience in the field of cardiovascular disease, is able to provide clients with drug discovery solutions to facilitate the development of novel ApoA-I modulators. If you are interested in our services, please do not hesitate to contact us.

1. Tao, X.; et al. Anti-inflammatory mechanism of Apolipoprotein A-I. Front Immunol. 2024, 15:1417270.