Vascular Genetics

Living reference work entry


Rare monogenetic diseases provide a unique window into the basic understanding of the resulting pathology. In a complex organ system such at the vasculature, identification of rare diseases that affect the architecture and/or cellular makeup of the vessel provides further insight into the underlying mechanisms that regulate homeostasis in healthy tissue.

More than just conduits for the movement of blood throughout the body, arteries contribute to the greater cardiovascular and general health of an individual via their ability to regulate blood pressure and heart rate. The wall of an artery consists of three layers: the tunica adventitia is the outer sheath which consists of fibroblasts, pericytes, and various resident immune cells, connective tissue, and collagen and elastic fibers; the tunica media, a thicker middle layer consisting of vascular smooth muscle cells, an abundant layer extracellular matrix, and elastic fibers; and the inner tunica intima, an elastic membrane upon which endothelial cells reside and have direct contact with blood. Below is a summary of monogenetic diseases that manifest the most common deleterious alterations in the vascular wall: atherosclerosis, aneurysms, and stiffening of the arteries. We have grouped these diseases by the general molecular mechanisms that are altered as a result of the identified genetic mutations. We believe that looking at disease pathologies through a molecular lens helps to understand the common mechanisms underlying vessel homeostasis and is beneficial for identifying potential therapeutic targets and treatment strategies.


Pulmonary Arterial Hypertension Vascular Calcification Hereditary Hemorrhagic Telangiectasia Arterial Calcification Thoracic Aortic Aneurysm 

Glossary of Terms


A weakening in the wall of an artery resulting in vessel enlargement.

Angiotensin-converting enzyme (ACE) inhibitors

A class of drugs used to treat hypertension and congestive heart failure.

Aortic dilation

Widening of the luminal diameter of the aorta.

Aortic dissection

Tearing of the inner wall of the aorta allowing blood to flow between the vessel wall layers forcing the layers to separate.


Proteins that bind to lipids to form lipoproteins.

Arterial calcification

Calcification of the arteries. May be located in the medial or the intima of the vessel.

Arteriovenous malformation

Abnormal direct connection between arteries and veins that circumvents the capillary system.


A class of drugs used to control cardiac arrhythmia, treat angina, and reduce high blood pressure.

Bicuspid aortic valve

Congenital condition whereby two of the three aortic valvular leaflets fuse, creating a bicuspid valve instead of a tricuspid valve.


A class of drugs that mimic the structure of pyrophosphate, are used to treat bone loss, and have shown in some cases to prevent and even reverse vascular calcification.


Lipoprotein particles that transport dietary lipids from the intestines to the rest of the body.


An abnormal amount of lipids (cholesterol and/or fat) in the blood.

Genetic locus

The chromosomal location of a gene or DNA sequence

HMG-CoA reductase

3-hydroxy-3-methylglutaryl-CoA reductase, the rate-limiting enzyme in cholesterol biosynthesis; converts HMG-CoA to mevalonic acid.


Mineral that is the main component of tooth enamel and bone and found in vascular calcification.


High blood levels of triglycerides.


Includes very-low-density lipoprotein (VLDL), low-density lipoprotein (LDL), intermediate-density lipoprotein (IDL), and high-density lipoprotein (HDL). These are soluble spherical particles made up of proteins and lipids that transport fats and cholesterol throughout the blood plasma.

Patent ductus arteriosus (PDA)

Congenital heart defect where the neonatal ductus arteriosus does not properly seal shut after birth.

Regurgitation, aortic and mitral

The leaking of the aortic or mitral valves of the heart results in aberrant blood flow.


A type of pharmaceutical drug that lowers cholesterol biosynthesis by inhibition of HMG-CoA reductase.


Small dilated blood vessels at or near the surface of the skin or mucous membranes.

Whole-exome sequencing (WES)

The sequencing of the parts of the genome encode for genes.


Discolored patches on the skin consisting of lipid deposits.


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© Springer-Verlag Berlin Heidelberg (outside the USA) 2014

Authors and Affiliations

  1. 1.Center for Molecular Medicine, Laboratory of Cardiovascular Regenerative MedicineNational Heart, Lung and Blood Institute, National Institutes of HealthBethesdaUSA

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