Treating Cardiovascular Disease with Liver Genome EngineeringHurley, Ayrea; Lagor, William R.
doi: 10.1007/s11883-022-00986-zpmid: 35230602
Purpose of ReviewThis review examines recent progress in somatic genome editing for cardiovascular disease. We briefly highlight new gene editing approaches, delivery systems, and potential targets in the liver.Recent FindingsIn recent years, new editing and delivery systems have been applied successfully in model organisms to modify genes within hepatocytes. Disruption of several genes has been shown to dramatically lower plasma cholesterol and triglyceride levels in mice as well as non-human primates. More precise modification of cardiovascular targets has also been achieved through homology-directed repair or base editing. Improved viral vectors and nanoparticle delivery systems are addressing important delivery challenges and helping to mitigate safety concerns.SummaryLiver-directed genome editing has the potential to cure both rare and common forms of cardiovascular disease. Exciting progress is already being made, including promising results from preclinical studies and the initiation of human gene therapy trials.
Imaging Approaches to the Diagnosis of Vascular DiseasesGimnich, Olga A.; Zil-E-Ali, Ahsan; Brunner, Gerd
doi: 10.1007/s11883-022-00988-xpmid: 35080717
Purpose of ReviewVascular imaging is a complex field including numerous modalities and imaging markers. This review is focused on important and recent findings in atherosclerotic carotid artery plaque imaging with an emphasis on developments in magnetic resonance imaging (MRI) and computed tomography (CT).Recent FindingsRecent evidence shows that carotid plaque characteristics and not only established measures of carotid plaque burden and stenosis are associated independently with cardiovascular outcomes. On carotid MRI, the presence of a lipid-rich necrotic core (LRNC) has been associated with incident cardiovascular disease (CVD) events independent of wall thickness, a traditional measure of plaque burden. On carotid MRI, intraplaque hemorrhage (IPH) presence has been identified as an independent predictor of stroke. The presence of a fissured carotid fibrous cap has been associated with contrast enhancement on CT angiography imaging.SummaryCarotid artery plaque characteristics have been associated with incident CVD events, and advanced plaque imaging techniques may gain additional prominence in the clinical treatment decision process.
Lipids: a Potential Molecular Pathway Towards Diastolic Dysfunction in Youth-Onset Type 2 DiabetesShah, Amy S.; Sadayappan, Sakthivel; Urbina, Elaine M.
doi: 10.1007/s11883-022-00989-wpmid: 35080716
Purpose of the ReviewObesity and type 2 diabetes (T2D) with onset in youth are emerging public health concerns. Youth with obesity and T2D are at risk for the development of heart failure with preserved ejection fraction (HFpEF) due to diabetes-related cardiomyopathy with evidence of precursor stages, namely diastolic dysfunction, present in youth. We review the literature regarding diastolic dysfunction in youth with obesity and T2D; discuss the potential mechanisms including the role of lipids, contractile proteins and their post-translational modifications, and conclude with studies to guide future treatments.Recent FindingsThe diabetes milieu namely hyperglycemia, hyperinsulinemia, and lipotoxicity favor development of diastolic dysfunction and HFpEF. Recent studies show HFpEF is associated with slow left ventricular relaxation and sarcomere stiffness induced by reduced calcium (Ca2+) and β-adrenergic responses.SummaryThere are currently no effective therapies available for treating HFpEF. Targeting the sarcomere is an area of ongoing research.
A Nutrigenetic Update on CETP Gene–Diet Interactions on Lipid-Related OutcomesWuni, Ramatu; Kuhnle, Gunter G. C.; Wynn-Jones, Alexandra Azzari; Vimaleswaran, Karani Santhanakrishnan
doi: 10.1007/s11883-022-00987-ypmid: 35098451
Purpose of ReviewAn abnormal lipid profile is considered a main risk factor for cardiovascular diseases and evidence suggests that single nucleotide polymorphisms (SNPs) in the cholesteryl ester transfer protein (CETP) gene contribute to variations in lipid levels in response to dietary intake. The objective of this review was to identify and discuss nutrigenetic studies assessing the interactions between CETP SNPs and dietary factors on blood lipids.Recent FindingsRelevant articles were obtained through a literature search of PubMed and Google Scholar through to July 2021. An article was included if it examined an interaction between CETP SNPs and dietary factors on blood lipids. From 49 eligible nutrigenetic studies, 27 studies reported significant interactions between 8 CETP SNPs and 17 dietary factors on blood lipids in 18 ethnicities. The discrepancies in the study findings could be attributed to genetic heterogeneity, and differences in sample size, study design, lifestyle and measurement of dietary intake. The most extensively studied ethnicities were those of Caucasian populations and majority of the studies reported an interaction with dietary fat intake. The rs708272 (TaqIB) was the most widely studied CETP SNP, where ‘B1’ allele was associated with higher CETP activity, resulting in lower high-density lipoprotein cholesterol and higher serum triglycerides under the influence of high dietary fat intake.SummaryOverall, the findings suggest that CETP SNPs might alter blood lipid profiles by modifying responses to diet, but further large studies in multiple ethnic groups are warranted to identify individuals at risk of adverse lipid response to diet.