Research News

Chronic venous insufficiency often manifests as varicose veins, a common condition that is easy to spot: swollen, bulging veins around the legs and ankles. Doctors know what is happening clinically, but not what is happening inside the vein – which means that the true understanding of the disease and its effects are somewhat limited.

New research published in Vascular Medicine from the lab of Scott Cameron, MD, PhD, provides scientists and physicians with insight into the biology of varicose veins. Anu Aggarwal, PhD, a research associate in Dr. Cameron’s lab and first author on the paper, used transcriptomics to measure gene expression inside the vein wall and characterize the biological pathways of the disease.

“Our transcriptomic study revealed that there is an active component to this disease,” Dr. Aggarwal says. “It’s much more than visible changes on the surface of the veins. The study shows that gene activity within the vein wall changes in varicose veins, providing new clues about disease development.”

The findings highlight possibilities for future study, and researchers hope that someday, varicose vein severity could be assessed through a blood test.

More than a cosmetic concern

Varicose veins develop when valves within the veins stop closing properly. This means blood flow refluxes (backs up instead of moving toward the heart) and pools in the legs. This leads to swelling, especially at the end of the day, a “heavy” and tired feeling, and restless legs.

Varicose veins are more common in women and often appear after pregnancy or menopause. There is no cure, but treatment options are available and depend on severity.

The disease falls under a larger umbrella: chronic venous insufficiency. As vein function continues to weaken and the disease progresses, the skin may appear brownish in color. Advanced stages of the disease may result in painful ulcers, infections or even life-threatening conditions like deep-vein thrombosis or pulmonary embolism.

A personal connection and curious approach

Understanding the biology of a disease helps researchers determine what drives it, which can then help them identify better ways to diagnose, prevent or treat it. Dr. Aggarwal was interested in studying varicose veins because she observed how the disease affected her mother. The Cameron Lab had varicose vein tissue samples available, and Dr. Aggarwal recognized an opportunity to discover how the veins differ biologically from healthy veins.

She and her team applied transcriptomics, or the study of active genes, using a customized panel of 770 genes involved in inflammation and fibrosis. Their goal was to identify differential genes and biological pathways in varicose veins. Using high-throughput technology, they noted increased activity in pathways involved in collagen production, connective tissue remodeling, blood vessel growth and fibrosis.

Dr. Aggarwal wondered if the same biological changes could be detected in blood samples, so the team tested 56 blood samples from Cleveland Clinic patients. The same collagen marker that registered high activity levels in the tissue samples also correlated with measures of disease severity.

The researchers believe that in the future, fragments of the collagen protein could eventually be studied as a potential blood-based biomarker for varicose veins. Though the disease is typically diagnosed with a physical exam or an ultrasound of the vein, the Cameron Lab sees possibilities for deeper assessment using minimally invasive measures.

“This is an important, hypothesis-generating study that characterizes vein diseases in a way many didn’t think of before,” Dr. Cameron says. “Vein diseases don’t have the same cultural or medical visibility as diseases involving the arteries, heart or brain – but now that we see more about its active process, we can design larger studies focused on diagnosis and treatment.”