| First Author | Luo R | Year | 2015 |
| Journal | Hypertension | Volume | 66 |
| Issue | 1 | Pages | 75-84 |
| PubMed ID | 25987665 | Mgi Jnum | J:280207 |
| Mgi Id | MGI:6369154 | Doi | 10.1161/HYPERTENSIONAHA.115.05578 |
| Citation | Luo R, et al. (2015) Elevated Endothelial Hypoxia-Inducible Factor-1alpha Contributes to Glomerular Injury and Promotes Hypertensive Chronic Kidney Disease. Hypertension 66(1):75-84 |
| abstractText | Hypertensive chronic kidney disease is one of the most prevalent medical conditions with high morbidity and mortality in the United States and worldwide. However, early events initiating the progression to hypertensive chronic kidney disease are poorly understood. We hypothesized that elevated endothelial hypoxia-inducible factor-1alpha (HIF-1alpha) is a common early insult triggering initial glomerular injury leading to hypertensive chronic kidney disease. To test our hypothesis, we used an angiotensin II infusion model of hypertensive chronic kidney disease to determine the specific cell type and mechanisms responsible for elevation of HIF-1alpha and its role in the progression of hypertensive chronic kidney disease. Genetic studies coupled with reverse transcription polymerase chain reaction profiling revealed that elevated endothelial HIF-1alpha is essential to initiate glomerular injury and progression to renal fibrosis by the transcriptional activation of genes encoding multiple vasoactive proteins. Mechanistically, we found that endothelial HIF-1alpha gene expression was induced by angiotensin II in a nuclear factor-kappaB-dependent manner. Finally, we discovered reciprocal positive transcriptional regulation of endothelial Hif-1alpha and Nf-kappab genes is a key driving force for their persistent activation and disease progression. Overall, our findings revealed that the stimulation of HIF-1alpha gene expression in endothelial cells is detrimental to induce kidney injury, hypertension, and disease progression. Our findings highlight early diagnostic opportunities and therapeutic approaches for hypertensive chronic kidney disease. |
