Cardiovascular Diseases

Atherosclerosis

Atherosclerosis is a disease of the blood vessels that is characterized by constant low-grade inflammation and the formation of dangerous blockages in medium and large vessels, which are called atherosclerotic plaques.

Atherosclerosis is a major cause of cardiovascular disease and death in many countries including the United States.

Cardiovascular diseases are closely linked with other conditions such as:

• Metabolic problems, like diabetes
• Autoimmune disorders, such as Rheumatoid arthritis
• Neuroimmunological disorders
• Stress
• Unhealthy sleep

How these factors make atherosclerosis worse is not well understood.

CINID's unique collaboration allows researchers to best investigate interactions between the immune system, vasculature and brain activities. The goal is to better understand how these systems interact, which would ultimately open new avenues to develop therapies and medications.

Atherosclerosis Working Group

• Elena Galkina, Ph.D.
• Larry D. Sanford, Ph.D.
• Laurie L. Wellman, Ph.D.

Heart Failure

Heart failure occurs when the heart cannot pump enough blood to meet the body's needs. This may be because the heart is too weak or stiff to fill and pump blood properly.

There are two main types  of heart failue:

• Heart Failure with Reduced Ejection Fraction (HFrEF) – the heart's pumping ability is weakened.
• Heart Failure with Preserved Ejection Fraction (HFpEF) – the heart is stiff and doesn't fill correctly.

Our laboratory studies the underlying mechanism of HFpEF using different mouse models. 

What causes HFpEF?

HFpEF occurs when the heart's ventricles become stiff and cannot relax properly. This results in impaired heart filling, even though the ejection fraction (the percentage of blood pumped out with each heartbeat) is normal.

The primary causes of HFpEF include:

• Hypertension: Chronic high blood pressure leads to thickening (hypertrophy) and stiffening of the heart muscle.
• Aging: Aging causes the natural stiffening of the heart muscle.
• Obesity: Excess weight increases the workload on the heart, contributing to diastolic dysfunction.
• Diabetes: Damages heart tissue, leading to stiffness and impaired relaxation.
• Chronic kidney disease: Alters fluid balance and heart function.
• Atrial fibrillation: Irregular heart rhythms reduce the heart's ability to fill correctly.

These conditions promote stiffening of the heart, making it harder for the ventricles to relax and fill with blood during diastole.

Our objectives

Our primary objective is to uncover the underlying mechanisms of HFpEF to enhance our understanding and facilitate the development of translational studies and therapeutic strategies.

We focus on:

• Inflammation
• Neuroinflammation
• Oxidative stress (when the body has too many free radicals and not enough antioxidants to neutralize them)
• The unfolded protein response (UPR), a cellular stress response to misfolded proteins
• How sleep disorders aggravate HFpEF pathogenesis through neuro-inflammation

Heart Failure Working Group

• Khalid Matrougui, Ph.D
• Larry D. Sanford, Ph.D.