Research

MatLab Research in Lay Terms
Scientists agree that long-term inflammation may be an important cause of high blood pressure or hypertension. We study lupus, an autoimmune disease that has both inflammation and a high percentage of hypertension, in hopes to reveal how long-term inflammation can lead to increases in blood pressure. We are currently studying how broken communication between the nervous system and the immune system may help contribute to inflammation in lupus hypertension using mice with the disease. Our research will lead to important information about the development, maintenance and treatment of both hypertension and lupus.

Current 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/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, renal injury, inflammation, neuro-immune, cholinergic anti-inflammatory pathway, hypothalamic-pituitary-adrenal (HPA) axis, kidney, vagus nerve, autonomic nervous system