Racial Disparities in Cardiovascular Risk and Cardiovascular Care in Women.

PURPOSE OF REVIEW: Research on sex and gender aspects cardiovascular disease has contributed to a reduction in cardiovascular mortality in women. However, cardiovascular disease remains the leading cause of death of women in the United States. Disparities in cardiovascular risk and outcomes among women overall persist and are amplified for women of certain ethnic and racial subgroups. We review the evidence of racial and ethnic differences in cardiovascular risk and care among women and describe a path forward to achieve equitable cardiovascular care for women of racial and ethnic minority groups. RECENT FINDINGS: There is a disproportionate effect on cardiovascular outcomes in women and certain racial and ethnic groups in part due to disparities in triage, diagnosis, treatment, which lead to amplification of inequalities in women of minority racial and ethnic background. Data suggest gender and racial bias, underappreciation of nontraditional risk factors, underrepresentation of women in clinical trials and undertreatment of disease contributes to persistent differences in cardiovascular disease outcomes in women of color. Understanding the myriad of factors that contribute to increased cardiovascular risk, and disparities in treatment and outcomes among women from racial/ethnic minority backgrounds is imperative to improving cardiovascular care for this patient population.

The Role of Replication Clamp-Loader Protein HolC of Escherichia coli in Overcoming Replication/Transcription Conflicts.

In Escherichia coli, DNA replication is catalyzed by an assembly of proteins, the DNA polymerase III holoenzyme. This complex includes the polymerase and proofreading subunits, the processivity clamp, and clamp loader complex. The holC gene encodes an accessory protein (known as χ) to the core clamp loader complex and is the only protein of the holoenzyme that binds to single-strand DNA binding protein, SSB. HolC is not essential for viability, although mutants show growth impairment, genetic instability, and sensitivity to DNA damaging agents. In this study, we isolate spontaneous suppressor mutants in a ΔholC strain and identify these by whole-genome sequencing. Some suppressors are alleles of RNA polymerase, suggesting that transcription is problematic for holC mutant strains, or alleles of sspA, encoding stringent starvation protein. Using a conditional holC plasmid, we examine factors affecting transcription elongation and termination for synergistic or suppressive effects on holC mutant phenotypes. Alleles of RpoA (α), RpoB (ß), and RpoC (ß') RNA polymerase holoenzyme can partially suppress loss of HolC. In contrast, mutations in transcription factors DksA and NusA enhanced the inviability of holC mutants. HolC mutants showed enhanced sensitivity to bicyclomycin, a specific inhibitor of Rho-dependent termination. Bicyclomycin also reverses suppression of holC by rpoA, rpoC, and sspA An inversion of the highly expressed rrnA operon exacerbates the growth defects of holC mutants. We propose that transcription complexes block replication in holC mutants and that Rho-dependent transcriptional termination and DksA function are particularly important to sustain viability and chromosome integrity.IMPORTANCE Transcription elongation complexes present an impediment to DNA replication. We provide evidence that one component of the replication clamp loader complex, HolC, of Escherichia coli is required to overcome these blocks. This genetic study of transcription factor effects on holC growth defects implicates Rho-dependent transcriptional termination and DksA function as critical. It also implicates, for the first time, a role of SspA, stringent starvation protein, in avoidance or tolerance of replication/replication conflicts. We speculate that HolC helps avoid or resolve collisions between replication and transcription complexes, which become toxic in HolC's absence.