Usage Information
Abstract
Insulin resistance impairs benefits of lipid-lowering treatment, as evidenced by higher cardiovascular disease risk in individuals with type 2 diabetes versus those without. Because platelet activity is higher in insulin-resistant patients and promotes atherosclerosis progression, we questioned whether platelets impair inflammation resolution in plaques during lipid lowering. In mice with obesity and insulin resistance, we induced advanced plaques and then implemented lipid lowering to promote atherosclerotic plaque inflammation resolution. Concurrently, mice were treated with either platelet-depleting or control antibodies for 3 weeks. Platelet activation and insulin resistance were unaffected by lipid lowering. Both antibody-treated groups showed reduced plaque macrophages, but plaque cellular and structural composition differed. In platelet-depleted mice, single-cell RNA-seq revealed dampened inflammatory gene expression in plaque macrophages and an expansion of a subset of Fcgr4+ macrophages having features of inflammation-resolving, phagocytic cells. Necrotic core size was smaller and collagen content greater, resembling stable human plaques. Consistent with the mouse results, clinical data showed that patients with lower platelet counts had decreased proinflammatory signaling pathways in circulating nonclassical monocytes after lipid lowering. These findings highlight that platelets hinder inflammation resolution in atherosclerosis during lipid-lowering treatment. Identifying novel platelet-targeted therapies following lipid-lowering treatment in individuals with insulin resistance may be a promising therapeutic approach to promote atherosclerotic plaque inflammation resolution.
Authors
Maria Laskou, Sofie Delbare, Michael Gildea, Ada Weinstock, Vitor De Moura Virginio, Maxwell La Forest, Franziska Krautter, Casey Donahoe, Letizia Amadori, Natalia Eberhardt, Tessa J. Barrett, Chiara Giannarelli, Jeffrey S. Berger, Edward A. Fisher
Usage data is cumulative from October 2025 through June 2026.
| Usage | JCI | PMC |
|---|---|---|
| Text version | 2,929 | 194 |
| 682 | 48 | |
| Figure | 486 | 0 |
| Table | 79 | 0 |
| Supplemental data | 371 | 23 |
| Citation downloads | 244 | 0 |
| Totals | 4,791 | 265 |
| Total Views | 5,056 | |
Usage information is collected from two different sources: this site (JCI) and Pubmed Central (PMC). JCI information (compiled daily) shows human readership based on methods we employ to screen out robotic usage. PMC information (aggregated monthly) is also similarly screened of robotic usage.
Various methods are used to distinguish robotic usage. For example, Google automatically scans articles to add to its search index and identifies itself as robotic; other services might not clearly identify themselves as robotic, or they are new or unknown as robotic. Because this activity can be misinterpreted as human readership, data may be re-processed periodically to reflect an improved understanding of robotic activity. Because of these factors, readers should consider usage information illustrative but subject to change.
