| First Author | Dai W | Year | 2023 |
| Journal | Science | Volume | 381 |
| Issue | 6661 | Pages | eadh5207 |
| PubMed ID | 37651538 | Mgi Jnum | J:340952 |
| Mgi Id | MGI:7531590 | Doi | 10.1126/science.adh5207 |
| Citation | Dai W, et al. (2023) Intracellular tPA-PAI-1 interaction determines VLDL assembly in hepatocytes. Science 381(6661):eadh5207 |
| abstractText | Apolipoprotein B (apoB)-lipoproteins initiate and promote atherosclerotic cardiovascular disease. Plasma tissue plasminogen activator (tPA) activity is negatively associated with atherogenic apoB-lipoprotein cholesterol levels in humans, but the mechanisms are unknown. We found that tPA, partially through the lysine-binding site on its Kringle 2 domain, binds to the N terminus of apoB, blocking the interaction between apoB and microsomal triglyceride transfer protein (MTP) in hepatocytes, thereby reducing very-low-density lipoprotein (VLDL) assembly and plasma apoB-lipoprotein cholesterol levels. Plasminogen activator inhibitor 1 (PAI-1) sequesters tPA away from apoB and increases VLDL assembly. Humans with PAI-1 deficiency have smaller VLDL particles and lower plasma levels of apoB-lipoprotein cholesterol. These results suggest a mechanism that fine-tunes VLDL assembly by intracellular interactions among tPA, PAI-1, and apoB in hepatocytes. |
