Sympathetic nervous system . Organ crosstalk . Chronic kidney disease . Heart failure . Hypertension . Cardiovascular Interventions
Translational Cardiology
Autonomic function and organ crosstalk in cardiovascular disease
The main research focus of our group is the autonomic nervous system and inter-organ crosstalk in cardiovascular disease. Chronic kidney disease and metabolic risk factors, such as obesity and diabetes, share a common pathophysiologic background, affecting nearly all organ systems. Notably, many of these processes are accompanied and complicated by a dysfunctional autonomic nervous system, dramatically impacting the incidence of cardiovascular morbidity and mortality. The growing burden of these often-confluent comorbidities has recently been recognized through the definition of a cardiovascular-kidney-metabolic syndrome. Our group seeks to understand how autonomic function can be modulated to prevent cardiovascular complications such as hypertension, arrhythmia, and heart failure. To this end, we have previously characterized rat models of metabolic syndrome and chronic kidney disease, revealing that suppression of sympathetic nerve activity prevents atrial fibrillation by inhibiting atrial structural and electrophysiological remodeling. Additionally, we found that renal neuromodulation reduces concentrations of uremic toxins in rats with chronic kidney disease, mitigating the development of left ventricular hypertrophy. Notably, the majority of these protective effects were independent of the well-established blood pressure-lowering effect of the procedure. In our most recent work, we discovered that renal denervation mitigates ischemic cardiomyopathy and attenuates chronic myocardial fibrosis through the alteration of cardiac macrophage composition. Another focus area of our group is improving medical therapies for the treatment of chronic cardiovascular disease. To better understand the interplay between medical and interventional therapies, spontaneously hypertensive rats underwent renal denervation and were randomized to receive antihypertensive medication. We observed that amlodipine and olmesartan achieved the largest blood pressure reductions.
Despite advances in medical and interventional therapies targeting diseases of the cardiovascular-kidney-metabolic syndrome, substantial complications such as arrhythmia, adverse myocardial remodeling, and heart failure remain challenging. Given that catheter-based renal denervation has become a safe and guideline-recommended treatment option for hypertension, the procedure itself or an extended multi-organ denervation approach might provide a novel therapeutic strategy in selected patients to modulate autonomic activity and preserve cardiac function. To improve the efficacy and safety of interventions, we characterized human sympathetic nerve distributions and functions not only in renal and carotid arteries but also in celiac and coronary arteries. With a strong focus on translating our results to clinical practice, we seek to establish novel interventional treatment opportunities, not only for cardiovascular diseases but also for contributory conditions such as metabolic syndrome.
