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New Frontiers in Cardiovascular Research

October 07, 2019
by Elisabeth Reitman

A long-standing question in developmental biology relates to how blood vessels form functional perfused networks. Anne Eichmann, PhD, Ensign Professor of Medicine, and her team hope to gain insight into this process.

Scientific Discoveries

Eichmann has received international recognition for her research exploring the factors that determine where the endothelial cells lining blood and lymphatic vessels grow. Her team showed that common molecular cues direct the growth of blood vessels and nerves.

In 2010 the Yale Cardiovascular Research Center (CVRC) recruited Eichmann from the Collège de France to join the School of Medicine. Eichmann’s lab aims to uncover the cellular mechanisms and molecular factors which regulate endothelial cell behavior.

This research may be the key to preventing cardiovascular disease. For example, Eichmann co-authored a study published in the Journal of Cell Biology with Martin Schwartz, PhD, aimed at understanding how arteriovenous malformations’ (AVMs) development can lead to targeting therapies to reverse the growth of AVMs and even prevent them from forming. The research team studied an inherited disorder called hereditary hemorraghic telangiectasia (HHT). Mutations in two cell receptors for proteins in the blood called BMPs cause HHT. They learned that the receptor signal depends on the BMPs and the force from flowing blood. These deviations can prevent blood vessels from responding normally to blood flow. Understanding the development of abnormal blood vessels could lead to potential therapies.

A recent study, published in Nature Communications, may offer a new approach to combat abnormal conditions and diseases. The authors found that endophilin-A2, a protein that controls endocytosis, helps regulate cell migration and sprouting. The authors believe this research has the potential to manipulate blood vessel growth towards an infarcted tissue area or away from a malignant tumor. Insights from these two studies are critical to address medical needs across a spectrum of illnesses.

Specialized endothelial cells form a thin layer along the interior surfaces of both blood and lymphatic vessels, in all tissues in the body. “Blood vessel networks are of considerable size—about 60,000 miles of vessels are in every human being,” Eichmann says. Despite the vast presence of this tissue in the body, questions persist regarding their functional characteristics. Studies have shown that signals such as vascular endothelial growth factor (VEGF), from a VEGFR2 receptor help regulate angiogenesis, or the creation of new blood vessels from existing blood vessels. Eichmann hopes to discover how these mechanisms govern cellular patterns during vascular and lymphatic development.

When VEGF and other endothelial growth factors bind to their receptors on endothelial cells, it initiates chemical signals within these cells that promote growth. “Endothelial cells are endlessly fascinating. They normally have very slow turnover, but start proliferating very fast when wounds need healing, or when tumors grow. They form semi-permeable barriers between the blood and the tissues that control exchanges of blood-borne substances, and these develop in an organ- specific fashion,” Eichmann explains.

Other chemical signals, called angiogenesis inhibitors, interfere with blood vessel formation. When these signals become unbalanced, angiogenesis is a common factor underlying many diseases such as cancer, age-related blindness, diabetic ulcers, and cardiovascular disease. “Dysregulation of blood vessel growth is implicated in many diseases. Understanding how blood vessels grow and acquire their function motivates me every day in the lab.”

Award in Vascular Biology

This year, the North American Vascular Biology Organization (NAVBO) will recognize Eichmann for her outstanding achievements as a vascular biologist with the Judah Folkman Award in Vascular Biology. NAVBO presents mid-career professionals with an award named in Folkman’s honor. Considered a pioneer in the field of vascular biology, Folkman’s groundbreaking research contributed to the understanding of tumor growth.

On October 30, 2019, Eichmann will present her Folkman Award Lecture, “Guidance of Vascular Barrier Formation” at Vascular Biology 2019 in Pacific Grove, California.

In addition to this recent honor, Eichmann has won other awards, including a European Research Council Advanced Grant, Lillian Bettencourt Prize for Life Sciences, the Chevalier de L’ordre National du Mérite, an Inserm Research Award, and the Jean Bernard Award from the Medical Research Foundation, among others. Eichmann has served on the NIH CDD study section, Inserm Scientific Research Council, the European Research Council, and the Fondation Lefoulon Delalande fellowship board, and the editorial boards of Physiology Reviews and Endothelium. She is a NAVBO council member, and co-organizer of the 2020 NAVBO meeting in Newport, Rhode Island.

Submitted by Elisabeth Reitman on October 21, 2019