For many researchers, the questions that define a career begin in the laboratory. For Lauren Biwer, PhD, of Yale University, one of those questions became personal.
Biwer had already spent years studying blood pressure regulation when her sister experienced preeclampsia during pregnancy. Despite her background in cardiovascular physiology, Biwer realized there was much she did not know about the condition.
That realization sent her searching through the scientific literature.
What she found would ultimately help shape the direction of her research: not only are many of the mechanisms underlying preeclampsia still incompletely understood, but women who experience it also face an increased risk of cardiovascular disease later in life.
Today, Biwer's laboratory studies female cardiovascular disease and female-specific cardiovascular risk factors, with particular attention to how uncomplicated and complicated pregnancies can influence cardiovascular health long after pregnancy has ended.
At the center of that work is a deceptively simple question:
Looking Beyond Pregnancy
Preeclampsia is characterized by high blood pressure accompanied by organ damage during pregnancy. But for Biwer, understanding what happens during pregnancy is only part of the story.
Her laboratory is interested in what happens afterward.
Research has linked a history of preeclampsia with increased cardiovascular risk, including evidence of vascular aging, atherosclerosis and microvascular dysfunction. The challenge is determining exactly what connects the pregnancy complication to disease years later.
One possibility is that preeclampsia reveals cardiovascular risk that was already present. Another is that the condition itself causes changes that persist after pregnancy.
Biwer's laboratory is working to separate those possibilities.
Using animal models without pre-existing cardiovascular risk factors allows the researchers to create controlled comparisons in which one group experiences preeclampsia and another does not. Isolated vessel studies can then help determine whether changes are intrinsic to the vasculature and begin narrowing those effects down to endothelial cells, smooth muscle cells or particular signaling mechanisms.
For a condition in which many of the risk factors for preeclampsia overlap with those for cardiovascular disease, that ability to isolate variables can help researchers move beyond identifying an association and begin investigating the mechanisms behind it.
When the Expected Dysfunction Isn't There
One of the lessons vascular research continues to reinforce for Biwer is that biology does not always behave the way a hypothesis predicts.
Researchers may expect an artery exposed to a particular disease condition to demonstrate dysfunction. Sometimes, however, it functions normally.
Rather than making the experiment less interesting, Biwer sees those results as an illustration of the redundancy of the vascular system. Blood vessels have multiple mechanisms available to regulate constriction and dilation, meaning an artery may preserve its overall function even when the pathway it normally relies upon has changed.
As Biwer explained, vessels can still function normally while potentially using “a different pathway to get there.”
Those responses can also vary across the arterial tree. Microvessels and large conduit arteries may respond differently depending on disease context, pregnancy, sex and the vascular bed being investigated.
Understanding those differences is one reason functional vascular measurements remain central to Biwer's research.
Ten Arteries, One Bigger Picture
Inside the Biwer Lab, researchers use both wire and pressure myography to investigate vascular function.
The laboratory has two wire myograph setups with eight chambers in total, along with two pressure myograph chambers, giving the team the ability to potentially study as many as ten isolated arteries at once.
The two techniques provide complementary perspectives. Wire myography allows the team to evaluate multiple arteries and experimental conditions simultaneously, helping identify where deeper investigation may be warranted. Pressure myography is particularly useful in the lab's studies of myogenic tone.
The team has also used both approaches to investigate vessels such as uterine arteries, comparing how the same vascular bed behaves under wire and pressure myography and considering which technique is best suited to a particular research question.
For Biwer, however, there is also something fundamentally fascinating about the experiment itself.
She first learned pressure myography during her PhD and has carried vascular physiology throughout her scientific career. Even now, as an assistant professor, seeing a living artery respond outside the body has not lost its appeal.
On a pressure myograph, a vessel that is barely visible to the naked eye becomes a dynamic physiological system on the screen, visibly constricting and dilating as conditions change.
Beyond providing an important functional readout, being able to directly observe those responses remains one of the things Biwer finds most exciting about vascular physiology.
Connecting Mechanisms to Future Cardiovascular Risk
Ultimately, the laboratory's work is aimed at understanding what connects preeclampsia with cardiovascular disease later in life.
Biwer's research suggests that preeclampsia may produce residual cardiovascular effects or alter how the vascular system responds to future stressors. Determining the mechanisms responsible could eventually reveal molecules or pathways that help explain this increased risk.
Understanding which established pathways are altered could also help researchers determine whether existing cardiovascular medications may have a role in reducing risk following preeclampsia. At present, Biwer noted, there is no therapy specifically intended to prevent preeclampsia-associated cardiovascular disease after pregnancy.
There is also a more immediate objective: awareness.
For women who have experienced preeclampsia, understanding that their pregnancy history may have implications for future cardiovascular health can create an opportunity for more informed conversations with physicians and greater attention to cardiovascular risk.
Building a Lab and the Next Generation of Scientists
Biwer's laboratory has been open for less than three years, making the work about more than establishing a research program. It is also about building a team.
Moving from postdoctoral researcher to principal investigator brought an entirely different set of challenges. Decisions about experimental direction now sit alongside decisions about funding, hiring, training and mentoring.
Her approach is straightforward: continue showing up, remain resilient and keep making progress.
As her laboratory grows, training other scientists has also become one of the parts of academia she values most. Members of her lab have earned their own grants and learned techniques such as wire myography, allowing Biwer to watch them develop as independent researchers.
For her, helping scientists learn to think critically, approach scientific problems independently and master new experimental techniques represents another form of impact.
Her advice to young researchers reflects that same philosophy:
Asking What Remains After Preeclampsia
There is still a considerable distance between identifying a vascular mechanism in the laboratory and changing clinical care. But answering fundamental questions is where that translation begins.
By combining controlled disease models with functional measurements of isolated blood vessels, the Biwer Lab is working to understand whether preeclampsia itself leaves lasting changes within the cardiovascular system.
Those answers could ultimately help researchers better understand why a complication experienced during pregnancy may remain relevant to cardiovascular health years later.
For Biwer, it brings the research back to the question at the center of her work: