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Jenkins, K. W.

Publications and source records attributed to Jenkins, K. W..

2 recordsLinked to original sources

Microsurgical Isolation and Molecular Characterization of the Mouse Left Internal Mammary Artery: Insights into Natural Resistance to Atherosclerosis

Atherosclerosis develops unevenly across the vascular tree, yet the molecular basis for this regional susceptibility remains poorly defined. The left internal mammary artery (LIMA), the most durable conduit for coronary artery bypass (CABG) surgery, is uniquely resistant to atherosclerosis in humans; however, it has never been isolated or studied in mouse models, limiting mechanistic insight into atheroprotective pathways. Here, we establish the first method to identify and isolate the murine LIMA and generate the first transcriptomic atlas of this artery. Cross-species analyses of human and mouse LIMA reveal a conserved protective signature that distinguishes the LIMA from atheroprone vessels and uncover fundamental molecular differences that govern vascular resilience. This study presents a transformative experimental platform for dissecting the determinants of atheroprotection and identifying molecular targets to improve CABG graft performance and long-term cardiovascular outcomes.

physiology↗

The IQGAP1-Claudin Cell Junction Axis in Cisplatin-induced Kidney Damage

Kidney damage resulting from nephrotoxicity is a major side effect of chemotherapy. Cisplatin is an effective antineoplastic agent broadly used in oncology where it interferes with DNA replication in dividing cells, however, its mechanism in kidney damage remains unclear. We tested the hypothesis that cisplatin displaces cell-contact proteins such as IQGAP1-claudin complex in the kidney tubules, causing epithelial cell dissociation and kidney damage. Employing a multifaceted approach, using mutant analyses and optimal cisplatin dose, this hypothesis was tested in cell culture and iqgap1-/- mouse models. Cisplatin inhibited cell proliferation and migration in an IQGAP1-dependent manner, displaced IQGAP1 from cell junctions and altered the expression level of key junctional markers, including claudins 2/4/8 and nephrin. Similar effects were observed in animal models where cisplatin treatment and loss of IQGAP1 had additive effects. These functional outcomes are accounted for by suppression of Akt1/PKB survival and ERK1/2 proliferation signals and activation of JNK-GSK3{beta} stress and inflammatory signal, widely implicated in kidney injury. These findings present IQGAP1-claudin axis as biomarkers and therapeutic targets in kidney damage and pave the way for formulating new analogs that eliminate cisplatin adverse side effects while preserving its antineoplastic efficacy.

cell biology↗