How do additional diseases affect the Cardiovascular System? The Cardiovascular Research Institute (CVRI) at Mount Sinai Fuster Heart Hospital is dedicated to uncovering how the heart and circulatory system function within the body’s interconnected systems. Before a group of our philanthropic supporters, CVRI scientific experts recently shared updates on their groundbreaking research aimed at understanding how various medical conditions place stress on the heart and vascular system, ultimately helping improve outcomes for patients with complex heart disease.
With the generous support of our donors, CVRI is revolutionizing our understanding of the intricate connections between diseases like diabetes and kidney disease; and how viral infection reveals how inflammation and metabolism drive cardiovascular complications. With advancements in precision medicine, we aim to develop targeted treatments that address these root issues, minimizing side effects and optimizing patient outcomes.
Filip Swirski, PhD
Director, Cardiovascular Research Institute
Arthur and Janet C. Ross Professor of Medicine (Cardiology)
Professor of Diagnostic, Molecular and Interventional Radiology
Icahn School of Medicine at Mount Sinai
As we age, it’s inevitable that we accumulate more health issues, or what we call comorbidities. Some of these conditions may exist side by side without affecting each other—chronic back pain, for example, typically doesn’t impact asthma or depression. But what we’re discovering is that many diseases do interact and influence each other, particularly in the context of cardiovascular health. There is growing evidence linking heart disease to conditions like cancer (a field known as cardio-oncology), inflammatory bowel disease, neurodegenerative diseases such as Alzheimer’s, and of course, classic risk factors like obesity, diabetes, and hypertension. The question we’re trying to answer is why these links exist—how do these diseases “talk” to one another?
Several systems seem to connect these comorbidities at a biological level. For instance, the immune system and its inflammatory responses appear to play a central role, as does metabolism. The circulatory, hematopoietic (blood-forming), endocrine, and even nervous systems might also facilitate these connections. Our work at the Cardiovascular Research Institute dives into the cellular and molecular mechanisms behind these links. By understanding how inflammation, metabolic activity, and other systemic responses drive the interaction between diseases, we’re aiming to unlock new approaches to treatment. This research has far-reaching implications, from developing therapies that target specific pathways to potentially mitigating the cascade of health issues that often accompanies aging.
One of our projects focuses on how influenza infections exacerbate heart disease. We’ve observed that people with the flu have a significantly higher risk of heart attack or heart failure, especially if they already have underlying cardiovascular issues. Our findings suggest that influenza exploits circulating immune cells, which act as Trojan horses, delivering the virus directly to the heart. This discovery points to inflammation as a key factor in viral-induced heart damage, and we’re now exploring ways to allow the immune system to combat the virus in the lungs while protecting the heart. The ultimate goal is precision medicine—targeted interventions that can limit the damage from comorbidities without broad, unintended effects. This precision approach could transform how we manage these interconnected diseases, improving outcomes by treating the root causes at a molecular level.
Leigh Goedeke, PhD
Assistant Professor, Medicine, Cardiology, Endocrinology, Diabetes and Bone Disease
Icahn School of Medicine at Mount Sinai
In my lab, we’re deeply focused on understanding how dysregulated metabolism contributes to chronic diseases, especially diabetes and cardiovascular disease. When I talk about metabolism, I mean the complex, life-sustaining chemical reactions that convert nutrients from our diet—carbohydrates, proteins, and fats—into energy or molecules our cells need. This process is highly regulated within our cells and at a broader level to maintain health, but when it’s dysregulated, it can lead to conditions like diabetes. In type 1 diabetes, the body can’t produce insulin, whereas, in type 2 diabetes, our cells become resistant to insulin, which leads to high blood sugar levels over time. This is critical because type 2 diabetes, affecting millions in the U.S., significantly raises the risk of cardiovascular issues such as heart attacks, heart failure, and stroke.
We’re particularly interested in how various risk factors in type 2 diabetes—such as high blood pressure, cholesterol, and inflammation—contribute to cardiovascular disease. Beyond this, we’ve observed that metabolic changes in specific tissues like the liver and heart can exacerbate cardiovascular risks. For example, fat accumulation and dysfunctional mitochondria in the liver can lead to excess glucose and lipid production, which raises blood sugar and promotes atherosclerosis. Additionally, we’ve identified certain harmful signaling metabolites generated by dysfunctional mitochondria in the liver that not only trigger local insulin resistance and inflammation but also travel through the bloodstream to affect other organs, including the heart. By collaborating with scientists across the CVRI, we’re exploring how these circulating metabolites might predict cardiovascular risks in patients with diabetes and testing how they drive inflammation and damage in different organs.
One exciting avenue we’re pursuing is an oral compound known as a controlled metabolic accelerator, which mimics a natural process called mitochondrial uncoupling. In our animal studies, this compound has shown promising results: it leads to fat-specific weight loss, improves glycemic control and insulin resistance, and reduces cardiovascular disease in models of obesity. By digging into the mechanisms of how this compound works, we hope to develop new treatment options that can address both diabetes and cardiovascular disease more effectively. The collaboration and integration of different expertise at CVRI allow us to study these interconnected processes holistically, aiming for breakthroughs that can truly transform patient outcomes.
Susmita Sahoo, PhD
Associate Professor, Medicine, Cardiology
Icahn School of Medicine at Mount Sinai
In my lab, we focus on understanding why patients with type 1 diabetes and those with advanced kidney disease are so prone to developing heart failure. These individuals experience heart failure at much higher rates than others, often succumbing to it rather than their primary illness. This phenomenon is not fully understood by clinicians, who currently lack treatments specifically for the heart complications in these patients. To investigate, we collaborate with nephrologists and endocrinologists to gather blood samples from hundreds of patients, comparing these with samples from healthy individuals. Our goal is to examine molecules within the blood that may explain why these patients develop heart failure, using heart cells in lab conditions to observe the impacts of disease-specific particles.
A critical focus is on extracellular vesicles (EVs) found in everyone’s blood, which act as molecular couriers. In our research, we’ve found that EVs from patients with kidney disease or diabetes carry damaging microRNAs from affected organs to the heart, influencing heart cells negatively. Using advanced sequencing, we analyze these microRNAs to identify which ones cause specific damage, whether in cultured heart cells or in live animal models. By pinpointing harmful microRNAs, we hope to develop diagnostic tools that can detect heart failure risk early—before symptoms appear. Additionally, this research paves the way for treatments tailored specifically to heart failure in patients with kidney disease or type 1 diabetes.
Our goal is to move towards precision medicine by developing diagnostics and therapies that target disease-specific factors, potentially more effective than general treatments like statins or SGLT2 inhibitors. We’re excited about the possibility of eventually partnering with pharmaceutical companies to bring these targeted therapies and diagnostic kits to clinical use. This work is possible thanks to a multidisciplinary effort, involving data scientists and lab teams who assist in processing and analyzing extensive data, with the supportive, collaborative environment at CVRI allowing us to push the boundaries in understanding and treating these complex heart conditions.