Investigators at UCLA working on the vascular side of cardiovascular disease know the blood vessel system is not just plumbing. In fact, our scientists are leading the way in understanding the difficult and fascinating extent to which our vascular systems differ, and the implications for preventing and curing vascular disease.
Dr. Luisa Iruela-Arispe
The arteries, veins and capillaries are amazingly complicated. “They are pipes, but there is a lot of power in those pipes,” says Dr. Luisa Iruela-Arispe, professor and vice-chair of Molecular, Cell & Developmental Biology
She notes that:
Tumor angiogenesis (Image courtesty of Iruela-Arispe Lab)
Dr. Iruela-Arispe is among a group of UCLA researchers focused on revealing the molecular mechanisms of how blood vessels develop.
This basic information may be used clinically to enhance the growth of blood vessels, such as for treatment of heart attacks or for wound healing, or to prevent growth, in the case of cancer. For example, cancer cannot spread without actually getting inside a blood vessel and then exiting it.
A postdoctoral physician researcher in her lab, Dr. Georg Hilfenhaus, has found that essentially, tumors “tickle” blood vessels. Also, the vessels respond by opening to let tumor cells in or out and in experiments, compounds actually seal the endothelium – the lining of the vessel. This sealant makes vessels impermeable to penetration by tumor cells.
The complexity of the vascular system can be seen in the case of young adults who were “blue babies” at birth – lacking enough oxygen to feed their bodies.
Over decades of research, doctors have found that:
One explanation for variability in vascular biology may be linked to nitric oxide, long a topic of research at UCLA. In fact, Dr. Louis Ignarro, now professor emeritus in molecular and medical pharmacology, received the Nobel Prize in Physiology/Medicine in 1998 for his work demonstrating the signaling properties of nitric oxide (NO).
Dr. Linda Cai
A question facing cardiology experts is whether an enzyme, endothelial nitric oxide synthase (eNOS), plays a positive or negative role in regulating the innermost lining of blood vessels, says Dr. Linda Cai, professor of anesthesiology and medicine (cardiology) and director of the Department of Anesthesiology’s Translational Research Program.
Dr. Cai’s team has made several discoveries about eNOS:
Dr. Cai and colleagues are now conducting human studies to reveal underlying mechanisms of eNOS dysfunction and to develop new therapies in a preclinical setting.
Many common diseases involve chronic inflammation, but in vascular disease, inflammation is key.
Dr. Jake Lusis, who studies the complex genetic traits underlying cardiovascular and metabolic disorders, lays out the connection:
UCLA researchers are studying how common foodstuffs harm blood vessels. This work is part of our efforts to expand the understanding of the interactions between nature and nurture – genes and the environment.
Dr. Lusis, in collaboration with investigators from Cleveland Clinic, has discovered how the gut microbiome can cause inflammation in the heart. Articles published in Cell in December 2015 and in the Journal of the American Heart Association in February 2016 show:
This research is just the beginning of learning how gut bacteria can protect the heart.
Another group of scientists has demonstrated how tweaking another food – actually a fruit – can improve a mouse’s cholesterol profile.
Researchers at UCLA conducted experiments in mice bred to develop inflammation and atherosclerosis. In these experiments:
According to Dr. Alan Fogelman, chair of Medicine and director of the Atherosclerosis Research Unit at the David Geffen School of Medicine, researchers are still trying to determine exactly how the peptide functions in animals, so don’t expect HDL tomatoes in the supermarket anytime soon. Still, the study is the first report in which a peptide has been engineered into food to reduce plaques and inflammation in the blood vessels of those who eat it.
UCLA research has helped to identify the process that underlies “hardening” of blood vessels.
It has long been known that bone tissue and even marrow can form in the walls of human arteries, usually near cholesterol deposits.
Dr. Linda Demer
Previously, says Dr. Linda Demer, vice chair of Medicine, artery wall calcification was considered a passive degenerative process. Now, work in Demer’s lab and in others indicates that artery wall cells actively form calcium deposits in much the same way that skeletal bone cells form mineral.
Together with Dr. Yin Tintut, Dr. Demer directs the Cardiovascular Biomineralization Research Group. In collaboration with UCLA engineers, they found:
Whether calcium deposits protect against, or increase the likelihood of, rupture of coronary plaques – and resulting heart attacks – is a question debated in the cardiovascular disease research community. This research is essential because of the widespread prevalence of vascular calcification, which promotes heart failure and hypertension.
Dr. Tzung Hsiai
While Dr. Demer has used culture models to study plaque, the engineering side of cardiologist Dr. Tzung Hsiai, professor of bioengineering and medicine (Cardiology), favors a more direct approach. He wants to get into the heart and “look around” to identify the risks associated with plaque and blood clots.
Dr. Hsiai and his group have developed flexible sensors that assess the pattern of blood moving around arterial plaque. The sensors work this way:
The aim of Dr. Hsiai’s program is to use these sensors while a coronary angiogram is underway. (An angiogram is an X-ray image of the blood vessels that supply the heart. The image reveals which vessels are functioning normally and alerts the physician when a blockage is happening.)
Benefits of the sensors may include: