Our Research

MatLab Research in Lay Terms
Scientists agree that ongoing inflammation may be a major reason why some people have high blood pressure, also known as hypertension. We are researching a disease called lupus, which involves inflammation and often leads to high blood pressure, to understand how this inflammation can make blood pressure go up over time. Currently, we are studying mice with lupus to see how problems in the way the nervous system and immune system talk to each other might cause inflammation and high blood pressure. The goal of this research is to find important information that can help us understand and treat both high blood pressure and lupus.

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Our Fight Against Disease

Hypertension

Hypertension, or high blood pressure, is a major risk factor for cardiovascular disease, the number one killer in the world. We are interested in how inflammation, specifically inflammation in the kidneys, contributes to pathogenesis of hypertension and renal disease.

Lupus

Systemic lupus erythematosus is a chronic autoimmune inflammatory disorder that affects organs throughout the body. The inflammation accumulates in the kidneys--lupus nephritis--and can lead to chronic kidney disease. Cardiovascular disease is a major cause of death in patients with lupus.

Autoimmune Disease

Autoimmune diseases occur when the body attacks itself. The cause of these diseases are mostly unknown. There is a high prevalence of autoimmune diseases in women and minority groups.

Current Research Projects and Interests

Hypertension is one of the most prevalent disease processes in the US and, while it undoubtedly has a multifactorial etiology, recent studies support a prominent role for the immune system and chronic inflammation. It is critical that we understand mechanisms that may regulate this inflammation in order to identify new therapeutic targets.

~The autonomic nervous system is known to regulate immune/inflammatory responses. To determine whether this neuro-immune crosstalk is important in preventing the development of chronic inflammation, we utilize the disease model systemic lupus erythematosus (SLE). SLE is an autoimmune disorder characterized by a high prevalence of hypertension, which may be mediated by chronic renal vascular and parenchymal inflammation. The cholinergic anti-inflammatory pathway is an endogenous mechanism that regulates chronic inflammation and is mediated by the parasympathetic vagus nerve. The studies proposed will investigate whether reduced vagal tone contributes to aberrant inflammatory responses and subsequently the pathogenesis of hypertension in a clinically-relevant mouse model of lupus. These studies are funded by the National Institutes of Health (KWM).

~The cholinergic anti-inflammatory pathway may be a therapeutic target in SLE. Along with our NIH-funded studies investigating the potential of vagus nerve stimulation, we are now studying the potential of splenic nerve stimulation to reduce splenic and peripheral inflammation in mice with SLE. These studies are funded by the Department of Defense (KWM).

~The established hypothalamic-pituitary-adrenal (HPA) axis also suppresses inflammation upon activation and the subsequent release of cortisol. There is evidence that stimulation of this neuro-endocrine-immune pathway can be mediated through the parasysmpathetic vagus nerve. Studies have demonstrated that SLE patients have decreased heart rate variability, which indicates depressed vagal nerve activity and may correlate with disease severity. However, it is not known whether this decreased vagal nerve activity contributes to HPA axis dysregulation in SLE, nor whether these potential relationships contribute substantially to the development of chronic inflammation and hypertension in the setting of SLE. These studies are funded by the National Institutes of Health (KWM).

~Because we use a mouse model of SLE to answer questions regarding the role of inflammation in hypertension, we are in a unique position to apply our findings to understanding the pathogenesis of lupus. We are currently investigating how early life stressors along with seasonal and environmental factors impact the pathogenesis of SLE.

Studies in our lab utilize an integrative physiological approach, complemented by neurophysiological and immunological techniques, to address our significant and clinically relevant questions.

Key Words: hypertension, lupus, autoimmune disease, renal disease, cardiovascular disease, renal injury, inflammation, neuro-immune, cholinergic anti-inflammatory pathway, hypothalamic-pituitary-adrenal (HPA) axis, kidney, vagus nerve, autonomic nervous system, sex differences

Research Summary

Neuroimmune mechanisms involved in the pathogenesis of hypertension and other chronic inflammatory diseases

What is the role of functional nervous and immune system communication in health and disease? -- Studies funded by the National Institutes of Health