Objective
In this project we aim to investigate the role of circulating extracellular vesicles (EVs) from Type 1 Diabetes (T1D) patients in the pathogenesis of heart failure (HF). Based on our pilot data we believe that T1D-EVs, but not healthy control (HC)-EVs, have toxic effects on cardiac cells causing their death and impairing their function, thus causing progression to HF in T1D patients. The goal of our study is to determine whether T1D-EVs are indeed cytotoxic to cardiac cells using blood samples from patients at different stages of T1D and healthy control subjects and to decipher what specific molecules in the T1D-EVs induce this cytotoxic effect.
Background Rationale
Heart failure is a serious health issue that affects millions of people around the world. It happens when the heart cannot pump enough blood to meet what the body needs. People living with heart failure often feel tired, gasp, experience a poor quality of life, and have the risk of death increase by many-fold. Those who have diabetes are a lot more likely to develop heart failure than people without diabetes. People with T1D develop heart failure at a higher rate and the risk of death is even higher. Unfortunately, scientists do not understand why and how this happens. So, we cannot treat them as needed. Most large-scale clinical trials for HF have limited or even excluded individuals with T1D. HF is, thus, an important, but under-recognized and under-studied threat for T1D patients. Little is known about the reasons behind the higher incidence of HF in the T1D population. Moreover, why there is increased death from HF in T1D patients has not been investigated.
Extracellular vesicles (EVs) are tiny particles found in the blood, that are released from all types of cells in our body. These EVs work like little messengers, carrying biological molecules from one cell to another. The molecules inside EVs are similar to the cells that they come from. So, they can help us understand about the disease condition of the cells and contribute to the disease process.
Our proposal will test the novel concept that circulating EVs from T1D patients have cardiotoxic effects on the survival and function of heart cells. They will also identify cargo molecules in the T1D EVs that mediate this cytotoxic effect on heart cells.
Description of Project
Heart failure is a serious health issue that affects millions of people around the world. It happens when the heart cannot pump enough blood to meet what the body needs. People living with heart failure often feel tired, gasp, experience a poor quality of life, and have the risk of death increased by many fold. Those who have diabetes are a lot more likely to develop heart failure than people without diabetes. People who have type 1 diabetes (T1D), the pancreas does not make enough insulin to manage the sugar levels in the blood. These patients develop heart failure at a higher rate and the risk of death is even higher. Unfortunately, scientists do not understand why and how this happens. So, we cannot treat them as they need.
There are tiny particles called 'extracellular vesicles (EVs) found in the blood, that are released from all types of cells in our body. These EVs work like little messengers, carrying biological molecules from one cell to another. The molecules inside EVs are similar to the cells that they come from. So, they can help us understand about the disease condition of the cells and contribute to the disease process.
Here, we aim to study how the EVs in T1D patients contribute to heart failure. Experiments from our lab are one of the first to suggest that the EVs in T1D patient blood play a key role in heart failure. We want to solve how this happens. We will analyze blood samples from T1D patients at different stages of the disease. By using several advanced methods, we hope to find important molecules in EVs that harm the cells in the heart. Knowing what these molecules are and how do they cause heart failure will help us develop tools to detect heart failure early in T1D patients. These can also develop new therapy to cure the disease.
Anticipated Outcome
We will analyze blood samples from T1D patients at different stages of the disease and compare them to healthy control (HC) subjects. By using several advanced methods, we aim to discover the specific molecules in circulating T1D-EVs that harm the cells in the heart.
Knowing what these molecules are and how they cause heart failure (HF) will help us develop tools to detect heart failure early even before any formal diagnosis of HF in T1D patients. This knowledge can also be used to develop new therapy to cure the disease.
Relevance to T1D
To date, no T1D-specific risk factor that triggers HF at the cellular or molecular level has been identified, primarily due to the lack of systematic studies in these patients. This application addresses this critical knowledge gap by studying the direct effects of circulating EVs from T1D patients on the survival and contractile function of cardiac cells.
Our study holds great promise for discovery of T1D-specific biomarkers for early diagnosis, prognosis and therapeutics of HF in patients with T1D. Our discoveries will be beneficial to patients, clinicians and scientists.