Premature atherosclerosis: An analysis over 39 years in the Netherlands. Implications for young individuals in high-risk families.

Cardiovascular disease (CVD), especially atherosclerotic cardiovascular disease (ASCVD), is one of the most important disease problems in the world accounting for an estimated 18.6 million deaths globally. Although older individuals are more often affected, ASCVD event at a young age is of particular importance because of more healthy years lost.

Downregulation of Endothelial Plexin A4 Under Inflammatory Conditions Impairs Vascular Integrity.

Besides hyperlipidemia, inflammation is an important determinant in the initiation and the progression of atherosclerosis. As Neuroimmune Guidance Cues (NGCs) are emerging as regulators of atherosclerosis, we set out to investigate the expression and function of inflammation-regulated NGCs. NGC expression in human monocytes and endothelial cells was assessed using a publicly available RNA dataset.

Netrin-4 expression by human endothelial cells inhibits endothelial inflammation and senescence.

Netrin-4, recognized in neural and vascular development, is highly expressed by mature endothelial cells. The function of this netrin-4 in vascular biology after development has remained unclear. We found that the expression of netrin-4 is highly regulated in endothelial cells and is important for quiescent healthy endothelium.

Genetic variants in SUSD2 are associated with the risk of ischemic heart disease.

Background: Genetic factors partly determine the risk for premature myocardial infarction (MI).

Objectives: We report the identification of a novel rare genetic variant in a kindred with an autosomal dominant trait for premature MI and atherosclerosis and explored the association of a common nonsynonymous variant in the same gene with the risk of ischemic heart disease (IHD) in a population-based study.

Methods: Next-generation sequencing was performed in a small pedigree with premature MI or subclinical atherosclerosis.

EPH receptor B2 stimulates human monocyte adhesion and migration independently of its EphrinB ligands.

The molecular basis of atherosclerosis is not fully understood and mice studies have shown that Ephrins and EPH receptors play a role in the atherosclerotic process. We set out to assess the role for monocytic EPHB2 and its Ephrin ligands in human atherosclerosis and show a role for EPHB2 in monocyte functions independently of its EphrinB ligands. Immunohistochemical staining of human aortic sections at different stages of atherosclerosis showed that EPHB2 and its ligand EphrinB are expressed in atherosclerotic plaques and that expression proportionally increases with plaque severity.

The identification and function of a Netrin-1 mutation in a pedigree with premature atherosclerosis.

Background And Aims: Neuroimmune guidance cues have been shown to play a role in atherosclerosis, but their exact role in human pathophysiology is largely unknown. In the current study, we investigated the role of a c.1769G > T variant in Netrin-1 in (premature) atherosclerosis.

Netrin-1 and the Grade of Atherosclerosis Are Inversely Correlated in Humans.

Objective: Netrin-1 has been shown to play a role in the initiation of atherosclerosis in mice models. However, little is known about the role of Netrin-1 in humans. We set out to study whether Netrin-1 is associated with different stages of atherosclerosis.

Netrin Family: Role for Protein Isoforms in Cancer.

Netrins form a family of secreted and membrane-associated proteins. Netrins are involved in processes for axonal guidance, morphogenesis, and angiogenesis by regulating cell migration and survival. These processes are of special interest in tumor biology.

Understanding netrins and semaphorins in mature endothelial cell biology.

Netrins and semaphorins are known as neuronal guidance molecules that are important to the facilitate patterning of the nervous system in embryonic development. In recent years, their function has been broadened to guide development in other systems, including the vascular system, where netrins and semaphorins critically contribute to the development of the vascular system. Evidence is accumulating that these guidance cues are also of critical importance in the biology of the mature endothelium by regulating the maintenance of endothelial quiescence.

Molecular basis of familial hypercholesterolemia.

Purpose Of Review: To provide an overview about the molecular basis of familial hypercholesterolemia.

Recent Findings: Familial hypercholesterolemia is a common hereditary cause of premature coronary heart disease. It has been estimated that 1 in every 250 individuals has heterozygous familial hypercholesterolemia and that fewer than 1% of patients with familial hypercholesterolemia have been identified across the globe.

New Drugs for Atherosclerosis.

Atherosclerosis, the underlying process that ultimately leads to clinical cardiovascular disease (CVD), is caused by the multifactorial interaction of various conditions, and dyslipidemia is widely acknowledged as 1 of the crucial risk factors in this process. Statin drugs have been shown to decrease low-density lipoprotein cholesterol and CVD morbidity as well as mortality and are therefore pivotal in CVD prevention. Despite the use of statin drugs, CVD remains a leading cause of mortality worldwide, which suggests that additional lipid-lowering therapies are warranted.