Volume 1 Issue 2, February 2022

High frequency of depressed mood increases the risk of future cardiometabolic disease above that due to lifestyle factors and genetic susceptibility alone, raising new questions about risk management in individuals susceptible to depression.

The International Mouse Phenotyping Consortium releases cardiac phenotype characterization of almost 4,000 monogenic null mice. This impressive international effort reports 486 new genes associated with cardiac malfunction.

Barisano et al. discuss how vascular dysfunction caused by blood–brain barrier breakdown interacts with amyloid beta and tau AD biomarkers and may predict early cognitive impairment, dementia and Alzheimer’s disease.

Alan Tall and Jose Fuster review the latest advances in our knowledge of the function of clonal hematopoiesis in cardiovascular disease and discuss the translation of this knowledge into therapeutics.

Honigberg and colleagues analyzed the frequency of depressed mood in conjunction with polygenic risk scores for coronary artery disease (CAD), type 2 diabetes (T2D) and atrial fibrillation in the UK Biobank and showed that depressed mood was independently associated with a lower risk of CAD and T2D across the cardiometabolic polygenic risk spectrum.

Cerebral venous thrombosis (CVT) is a rare life-threatening disease of unknown etiology. Stegner et al. show that aberrant platelet activation through cooperative signaling of CLEC-2 and GPIIb/IIIa receptors triggers foudroyant CVT in mice and shed light on the molecular pathways of the disease pathogenesis.

Song and colleagues show that FDA-approved cough suppressant dextromethorphan could be used as an agonist of sigma non-opioid intracellular receptor 1 (SIGMAR1) to normalize the action potential in human cellular models and a mouse model of Timothy syndrome, a congenital disease with no available treatment. The researchers also show that dextromethorphan normalizes the action potential in human cellular models of two additional inherited cardiac arrhythmias: long QT syndrome types 1 and 2, which are caused by mutations in different genes.

In a multicenter research program coordinated by the International Mouse Phenotyping Consortium, Spielmann et al. analyze the cardiac function and structure in ~4,000 monogenic mutant mice and identify 705 mouse genes involved in cardiac function, 75% of which have not been previously linked to cardiac heritable disease in humans. Using the UK Biobank human data, the authors validate the link between cardiovascular disease and some of the newly identified genes to illustrate the resource value and potential of their mutant mouse collection.

Using large-scale single-nucleus transcriptomics, Nicin et al. report insights into human cardiac hypertrophy, caused by pressure overload, at single-cell resolution. The authors show that intercellular communication, particularly via the Eph receptor tyrosine kinase EPHB1, is impaired in human cardiomyopathy.