Cardiovascular Research Institute

Cells communicate across distances through extracellular vesicles (EVs)—tiny, membrane-covered packages that transport proteins, lipids, and nucleic acids between cells, tissues, and organs. EVs are smaller than one-hundredth the diameter of a red blood cell, yet they play vast roles in both normal physiology and disease. They can cross barriers like the blood-brain barrier, making them efficient mediators of disease propagation, including how cancers suppress the immune system and facilitate metastasis. EVs serve as valuable biomarkers and allow clinicians to monitor disease progression non-invasively over time.

We are exploring EVs' therapeutic potential. With efficient cellular uptake, low toxicity, and lack of immunogenicity, EVs and engineered synthetic bionanovesicles are being developed as delivery vehicles for genes, proteins, RNA, and gene-editing tools like CRISPR/Cas9. Encapsulating therapeutic viruses in EVs can also circumvent resistance from neutralizing antibodies, addressing a major challenge in gene therapy.

Fibromuscular dysplasia (FMD) and spontaneous coronary artery dissection (SCAD) are vascular conditions that disproportionately affect women and can lead to serious cardiovascular events. FMD involves abnormal cell growth in artery walls, while SCAD occurs when a tear forms in a coronary artery wall, disrupting blood flow to the heart. Mount Sinai investigators study the genetic, hormonal, and structural factors that contribute to these conditions, which are often underdiagnosed and poorly understood. By identifying the mechanisms underlying FMD and SCAD, we aim to improve diagnostic approaches and develop targeted therapies.

Modified mRNA (modRNA) therapeutics represent an innovative pharmaceutical technology with the capacity to create personalized medicines. At Mount Sinai, we pioneered the use of modRNA to treat heart disease. Our researchers were able to demonstrate that delivering beneficial VEGF-A modRNA at the time of myocardial infarction could promote cardiac protection and vascularization. Over the past decade, our researchers have shown that modified mRNA can temporarily alter non-regenerative gene expression in the heart, allowing brief regenerative capacity immediately after injury and promoting cardiac protection, vascularization, and regeneration following ischemia.

Hematopoiesis is the process by which blood cells are produced, primarily in the bone marrow. This system generates the immune cells, red blood cells, and platelets that circulate through the cardiovascular system. We are investigating how the hematopoietic system influences cardiovascular disease, particularly through the immune cells that drive inflammation in atherosclerosis, heart failure, and recovery from myocardial infarction. This work also explores how cardiovascular events and risk factors—like myocardial infarction, chronic stress, and poor diet—affect hematopoietic stem cell function and immune cell production.

Heart failure describes a group of diseases in which the heart cannot pump enough blood to meet the body's needs. There are two main types of chronic heart failure: heart failure with reduced ejection fraction (HFrEF), caused by diseases that reduce pump function, and heart failure with preserved ejection fraction (HFpEF), where pump function remains intact but the heart cannot store enough blood for effective circulation. At the Cardiovascular Research Institute, our researchers study disease pathophysiology, diagnosis, and treatments for both types.

Our HFrEF research examines cardiomyopathy, genetics, myocardial infarction, and molecular signaling in disease development. For HFpEF, which is closely associated with lifestyle-related disorders like hypertension and metabolic disease, we focus on the immune system's relationship to individual choices and environmental factors. Our therapeutic development employs gene therapy, tissue engineering, device therapy, and stem cell therapy—approaches tested in large animal models to promote clinical translation and improve survival and quality of life for patients living with heart failure.

Myocardial infarction—commonly known as heart attack—remains a major cause of death and disability. Many patients die from arrhythmia before reaching the hospital, and even those who receive prompt treatment may develop chronic heart failure due to reduced cardiac function. Institute researchers address this disease by studying pathological mechanisms, diagnostic methods, and therapeutic approaches.

To identify key processes in coronary artery disease, Mount Sinai investigators study lifestyle and environment, radiation and space biology, heart development, and cross-organ communication in systemic disease. We are exploring novel imaging approaches to diagnose coronary artery disease early, supporting timely treatment that can avert complications. Once myocardial infarction occurs, minimizing injury is crucial for limiting mortality and morbidity. We employ stem cell therapy, tissue bioengineering, gene therapy, and device therapy to prevent myocardial death, regenerate heart muscle, and support cardiac function.

Nanomedicine applies nanotechnology to medical challenges, using materials and devices at the molecular scale to diagnose, monitor, and treat disease. For cardiovascular medicine, this includes nanoparticles that can deliver drugs directly to diseased tissue, imaging agents that detect early disease, and biosensors that monitor cardiovascular function in real time.

We are developing nanoparticle-based therapies that target specific cells and tissues in the cardiovascular system, improving drug delivery while reducing side effects. This includes designing nanoparticles that can cross biological barriers, accumulate in atherosclerotic plaques, or deliver therapeutic agents to injured heart tissue after myocardial infarction. Nanomedicine also enables more precise diagnostics through enhanced imaging technologies and biosensors that detect biomarkers at extremely low concentrations.

Positron emission tomography (PET) imaging uses radioactive tracers to visualize metabolic processes and cellular activity in living tissue, providing unique insights into cardiovascular disease that other imaging modalities cannot capture. Mount Sinai researchers use advanced PET imaging to study inflammation, metabolism, and blood flow in the heart and blood vessels. Our investigators employ PET to track immune cell activity in atherosclerotic plaques, helping identify which plaques are most likely to rupture and cause heart attacks or strokes. PET imaging also reveals metabolic changes in heart failure, showing how the heart's energy production shifts in disease states and how therapies affect cardiac metabolism. This research is developing new PET tracers that target specific biological processes relevant to cardiovascular disease.

Sleep profoundly affects cardiovascular health, yet the mechanisms linking sleep disruption to heart disease are complex. Our researchers are investigating how sleep quality, duration, and timing influence immune function, metabolism, inflammation, and cardiovascular physiology. Our work examines how sleep deprivation and sleep disorders like sleep apnea affect cardiovascular risk factors, including blood pressure, glucose metabolism, and inflammatory markers. We study how poor sleep influences the progression of atherosclerosis, heart failure, and recovery from myocardial infarction at the molecular and cellular levels.

Space travel exposes astronauts to unique cardiovascular stressors, including microgravity, isolation, circadian disruption, and cosmic radiation. Mount Sinai researchers study how these extreme conditions affect the cardiovascular system, both to protect astronaut health during long-duration space missions and to gain insights into fundamental cardiovascular biology that apply to Earth-based medicine.

Our investigators use tissue engineering and microphysiologic systems to study how microgravity accelerates cardiovascular aging and how space-type radiation affects human cardiac tissue. These studies employ patient-specific cells and engineered tissues to measure cardiovascular risks and develop effective countermeasures for astronaut safety during exploratory missions to the Moon, Mars, and beyond. This research also reveals how environmental stressors affect cardiovascular function at the cellular and molecular levels, with implications for understanding disease processes on Earth.

Stem cells hold unique potential for cardiovascular medicine because of their ability to differentiate into specialized cell types and their capacity for self-renewal. Mount Sinai researchers work with multiple stem cell types, including induced pluripotent stem cells (iPSCs). Our investigators use iPSCs to study cardiovascular disease mechanisms, test new therapies, and develop regenerative approaches for damaged heart tissue. Patient-specific iPSCs allow us to create disease models that reflect individual genetic backgrounds, enabling personalized medicine approaches and drug screening tailored to specific patients or populations. Stem cell therapy also offers the potential to regenerate heart muscle after myocardial infarction or in heart failure—addressing the heart's limited natural regenerative capacity.

Chronic stress is a well-established risk factor for cardiovascular disease. Mount Sinai researchers investigate how stress affects the immune system, metabolism, inflammation, and cardiovascular physiology at the molecular and cellular levels. Our work examines how stress hormones and nervous system signaling influence atherosclerosis progression, myocardial infarction risk, and recovery from cardiac events. We study how chronic stress affects hematopoiesis—the production of immune cells—and how these cells contribute to inflammation in the cardiovascular system.

Tissue engineering combines living cells, material scaffolds, and biologically active molecules in specially designed bioreactors to create three-dimensional tissue surrogates for nearly every organ in the body. Cardiac tissue engineering is particularly challenging because heart muscle cells from patient biopsies have limited availability and cannot survive or proliferate in culture. Mount Sinai investigators have been pushing the boundaries of human cardiac tissue engineering for over a decade.

Our researchers are employing patient-specific human engineered cardiac tissue to seek a cure for familial heart disease related to phospholamban gene mutations. We are also pioneering microphysiologic systems that combine microfluidic chips with micro-scale tissue engineering, creating tube-like cardiovascular organoids that integrate multiple tissue types with heart-driven pulsatile flow. These systems are being used to study early human heart development, evaluate cardiovascular aging in microgravity aboard the International Space Station, measure cardiovascular risks from space radiation, and develop countermeasures for astronaut safety during long-term space missions.