Atherosclerosis and HIV: Exploring Cardiovascular Risks and Management.

The advent of antiretroviral therapy has markedly improved the life expectancy of individuals with HIV, leading to a shift in clinical focus from managing opportunistic infections to addressing chronic conditions, such as atherosclerotic cardiovascular disease (ASCVD). Emerging evidence highlights an elevated risk of ASCVD among people living with HIV, characterized by a higher incidence of acute myocardial infarction, ischemic stroke, and heart failure compared with the general population. This review examines the epidemiology, pathophysiology, and management of ASCVD in the context of HIV. It explores the interplay between HIV infection, antiretroviral therapy, and traditional cardiovascular risk factors, underscoring the need for comprehensive cardiovascular risk reduction strategies tailored to people living with HIV. Through synthesizing data from clinical trials, observational studies, and basic research, the review aims to enhance understanding of HIV-associated ASCVD and inform healthcare practices to improve the longevity and quality of life for this patient population.

Reprogrammable CRISPR/Cas9-based system for inducing site-specific DNA methylation.

Advances in sequencing technology allow researchers to map genome-wide changes in DNA methylation in development and disease. However, there is a lack of experimental tools to site-specifically manipulate DNA methylation to discern the functional consequences. We developed a CRISPR/Cas9 DNA methyltransferase 3A (DNMT3A) fusion to induce DNA methylation at specific loci in the genome. We induced DNA methylation at up to 50% of alleles for targeted CpG dinucleotides. DNA methylation levels peaked within 50 bp of the short guide RNA (sgRNA) binding site and between pairs of sgRNAs. We used our approach to target methylation across the entire CpG island at the CDKN2A promoter, three CpG dinucleotides at the ARF promoter, and the CpG island within the Cdkn1a promoter to decrease expression of the target gene. These tools permit mechanistic studies of DNA methylation and its role in guiding molecular processes that determine cellular fate.