Cardiovascular Disease in Patients With Systemic Lupus Erythematosus: Potential for Improved Primary Prevention With Statins.

Cardiovascular disease (CVD) is a significant cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). This is especially true in SLE patients with traditional CVD risk factors (eg, hypertension, hyperlipidemia, obesity) and disease-related risk factors (eg, increased SLE disease activity, elevated C-reactive protein levels, and antiphospholipid antibodies). The only guidelines in the primary prevention of CVD in SLE patients involve reducing traditional risk factors, but there are additional therapies that may be beneficial, including statin use. Current data on statin use for prevention of CVD in SLE patients are limited, but there have been some promising results. Statin use has been shown to be especially important in SLE patients for decreasing low-density lipoprotein levels and preventing CVD in hyperlipidemic patients. In addition, there is evidence suggesting that it may be beneficial to use statins in SLE patients with chronically elevated high-sensitivity C-reactive protein levels and antiphospholipid antibodies. It is important to continue to investigate the impact of statins on CVD in SLE patients, as they could significantly improve outcomes in patients with this disease.

A Genome-wide CRISPR Death Screen Identifies Genes Essential for Oxidative Phosphorylation.

Oxidative phosphorylation (OXPHOS) is the major pathway for ATP production in humans. Deficiencies in OXPHOS can arise from mutations in either mitochondrial or nuclear genomes and comprise the largest collection of inborn errors of metabolism. At present we lack a complete catalog of human genes and pathways essential for OXPHOS. Here we introduce a genome-wide CRISPR "death screen" that actively selects dying cells to reveal human genes required for OXPHOS, inspired by the classic observation that human cells deficient in OXPHOS survive in glucose but die in galactose. We report 191 high-confidence hits essential for OXPHOS, including 72 underlying known OXPHOS diseases. Our screen reveals a functional module consisting of NGRN, WBSCR16, RPUSD3, RPUSD4, TRUB2, and FASTKD2 that regulates the mitochondrial 16S rRNA and intra-mitochondrial translation. Our work yields a rich catalog of genes required for OXPHOS and, more generally, demonstrates the power of death screening for functional genomic analysis.