The multiple roles of CD36 in the development and progression of atherosclerosis?

1. What are the molecular structure and post-translational modification characteristics of CD36?

CD36 is an 88 kDa transmembrane glycoprotein belonging to the class B scavenger receptor family. Its gene is located on chromosome 7 (7q11.2), encoding a single polypeptide chain of 472 amino acids that forms a unique spatial conformation with two transmembrane domains, short cytoplasmic domains, and a large glycosylated extracellular domain. The synthesis, localization, and functional activity of CD36 are finely regulated by various post-translational modifications.

Ubiquitination primarily occurs at Lys472 and Lys469 residues in the N-terminus of CD36, with elevated ubiquitination levels in the presence of long-chain fatty acids. Parkin-mediated monoubiquitination enhances its stability, while USP14 mediates the deubiquitination process. Palmitoylation occurs at Cys3, Cys7, Cys464, and Cys466 residues, catalyzed by DHHC4/5 palmitoyltransferases. Phosphorylation mainly occurs at Thr93 and Ser237 residues, regulated by PKC, PKA, and IAP kinases. Additionally, there are 10 glycosylation sites in the extracellular domain of CD36. This complex modification network collectively regulates CD36's membrane localization, stability, and signal transduction capabilities, establishing the molecular basis for its multiple functions in atherosclerosis.

2. How does CD36 participate in endothelial cell dysfunction?

Endothelial dysfunction is the initiating factor in atherosclerosis. Studies show that CD36 is widely expressed on the surface of aortic endothelial cells, with significant upregulation under oxidized low-density lipoprotein (ox-LDL) stimulation or high-fat diet conditions. CD36 mediates the endocytic uptake of ox-LDL and other modified lipids, promoting lipid accumulation in the subendothelial space and thereby initiating early atherosclerotic lesions.

Molecular mechanism studies reveal that CD36-mediated lipid uptake is closely related to fatty acid metabolism. Fatty acid binding to CD36 can enhance ox-LDL uptake efficiency by increasing intracellular esterification rates, forming a positive feedback loop. Endothelial cell-specific CD36 knockout mice show reduced long-chain fatty acid transfer, improved glucose tolerance, and decreased cardiac lipid deposition, further confirming CD36's key role in endothelial lipid metabolism regulation. These findings suggest that targeting CD36 may be a potential strategy to improve endothelial dysfunction and delay atherosclerosis progression.

3. What role does CD36 play in vascular smooth muscle cell dysfunction?

Vascular smooth muscle cells (VSMCs) are crucial for maintaining vascular homeostasis. During atherosclerosis progression, CD36 expression on VSMCs is upregulated, participating in the regulation of lipid metabolism disorders and immune response dysregulation. ox-LDL can induce increased expression of granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in VSMCs through CD36 signaling pathways, while enhancing cell migration capacity, promoting VSMC migration from the media to the intima, leading to neointima formation and vascular wall thickening.

CD36-deficient VSMCs exhibit reduced proliferation capacity, associated with suppressed cyclin A expression. Additionally, as a pattern recognition receptor, CD36 participates in VSMC immune regulation, affecting arterial wall inflammatory responses. These findings suggest that targeting VSMC surface CD36 may be an important intervention direction for regulating vascular remodeling and inhibiting atherosclerosis progression.

4. How does CD36 regulate macrophage function to promote atherosclerosis?

Macrophages are the primary cell type in atherosclerotic plaques, and their transformation into foam cells through CD36-mediated ox-LDL uptake is a key step in plaque formation. ox-LDL upregulates CD36 expression by activating peroxisome proliferator-activated receptor γ (PPARγ), forming a positive feedback loop that promotes lipid accumulation.

CD36 signaling regulates macrophage function through multiple mechanisms: activating NADPH oxidase to promote reactive oxygen species (ROS) generation; regulating mitochondrial metabolic reprogramming, affecting macrophage polarization; modulating macrophage migration capacity, influencing their retention in plaques; participating in vimentin secretion and pro-inflammatory cytokine (e.g., TNF-α and IL-6) release. Studies show that CD36-deficient macrophages exhibit enhanced oxidative phosphorylation and M1 polarization under ox-LDL stimulation, while wild-type macrophages tend toward glycolytic metabolism. These findings reveal CD36's central role in macrophage inflammatory metabolic reprogramming.

5. What function does platelet CD36 have in thrombosis?

Platelet activation plays a key role in thrombus formation following atherosclerotic plaque rupture. As an important platelet surface receptor, CD36 binds to various endogenous and exogenous ligands, promoting high platelet activation through Src family kinases, Vav guanine nucleotide exchange factors, cGMP, and NADPH oxidase signaling pathways.

Research shows that advanced glycation end products accelerate thrombus formation through specific interactions with platelet CD36. CD36-deficient mice exhibit delayed occlusive thrombus formation in thrombosis models. Clinical studies also find significantly elevated platelet CD36 expression in coronary artery disease patients, and these platelets can promote monocyte polarization and foam cell formation in a CD36-dependent manner. These findings reveal platelet CD36's important role in atherosclerotic thrombotic complications.

6. What is the application value of rabbit anti-human CD36 antibody in atherosclerosis research?

As a specific research tool recognizing CD36 epitopes, rabbit anti-human CD36 antibody holds significant value in atherosclerosis mechanism studies and drug development. This antibody can be used for: detecting CD36 expression distribution in various vascular cell types through immunohistochemistry; analyzing CD36 expression levels in different cell populations using flow cytometry; studying CD36 interactions with downstream signaling molecules via co-immunoprecipitation; establishing CD36 functional blockade models to assess its role in atherosclerosis progression.

In translational research, this antibody can develop CD36-targeted therapeutic strategies, evaluate the impact of CD36 signal blockade on atherosclerosis progression; serve as a diagnostic tool to detect soluble CD36 levels, exploring its potential as an atherosclerosis biomarker; assist in studying associations between CD36 single nucleotide polymorphisms and disease susceptibility. With deepening understanding of CD36's complex mechanisms in atherosclerosis, rabbit anti-human CD36 antibody will continue providing powerful tool support for this important disease research.

7. Which manufacturers provide rabbit anti-human CD36 antibodies?

Hangzhou Start Biotech Co., Ltd. independently developed "Rabbit Anti-Human CD36 Antibody" (Product Name: Rabbit Anti-Human CD36 Antibody (S-1063-171), a high-specificity, high-affinity, and exceptionally stable multifunctional scavenger receptor detection tool. This product has been rigorously validated across multiple technical platforms including flow cytometry, Western Blot, and immunohistochemistry, holding significant application value in cross-disciplinary research areas such as lipid metabolism, platelet function, angiogenesis, and tumor immunology.

Professional Technical Support: We provide comprehensive product technical documentation, including specificity validation data, experimental protocols for various application platforms, and professional technical support, fully assisting customers in achieving breakthroughs in interdisciplinary research areas such as metabolism, cardiovascular, and tumor biology.

Hangzhou Start Biotech Co., Ltd. is committed to providing high-quality, high-value biological reagents and solutions for global innovative pharmaceutical companies and research institutions. For more details about "Rabbit Anti-Human CD36 Antibody" or to request sample testing, please contact us.

Product Information