Feil Family Brain & Mind Research Institute

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Faraco, Giuseppe - Iadecola Laboratory - Neurovascular Pathologies and Neurodegeneration

Giuseppe Faraco, MD, Ph.D.
Assistant Professor of Neuroscience

 

Overview

The brain is a major target of the end-organ damage produced by hypertension, and hypertension is a leading risk factor for stroke and dementia. Despite the benefits of anti-hypertensive therapy, the burden of disease caused by hypertension remains substantial, especially in the brain. Cerebral blood vessels are uniquely susceptible to the deleterious effects of hypertension, resulting in pathological alteration of the vascular wall and disruption of BBB permeability leading to major alterations in the composition of the brain microenvironment. Furthermore, we have discovered that hypertension disrupts neurovascular control mechanisms that assure an adequate cerebral blood supply. Loss of these vital homeostatic responses compromises the blood supply to the brain and increases the susceptibility of the brain to vascular insufficiency and ischemic damage.

How hypertension exerts these harmful effects is still uncertain, and elucidating the underlying mechanisms is a necessary step for developing new approaches to prevent stroke and dementia. Our research is particularly focused in elucidating the specific cellular targets through which hypertension alters neurovascular function, and their eventual link to cognitive impairment.

Over the last years, it has been shown that both the innate and the adaptive immune system play a role in the pathogenesis of hypertension and other cardiovascular diseases such as obesity and diabetes. Therefore, we are currently investigating whether peripheral or brain-resident immune cells contribute to the cerebrovascular alterations induced by hypertension and other cardiovascular risk factors.

Effect of hypertension on cerebral blood vessels (Hypertension, 62:810, 2013).

Achievements

-Scientist Development Grant Award from the American Heart Association (2015-2018) "Role of immune cells in Angiotensin II-mediated neurovascular dysfunction”

 

Selected Publications

Faraco G, Brea D, Garcia-Bonilla L, Wang G, Racchumi G, Chang H, Buendia I, Santisteban MM, Segarra SG, Koizumi K, Sugiyama Y, Murphy M, Voss H, Anrather J, Iadecola C. (2018). Dietary salt promotes neurovascular and cognitive dysfunction through a gut-initiated TH17 response. Nat Neurosci. 21:240, 2018

Faraco G, Park L, Anrather J, Iadecola C. Brain perivascular macrophages: characterization and functional roles in health and disease. J Mol Med (Berl). 95:1143, 2017

Faraco G, Sugiyama Y, Lane D, Garcia-Bonilla L, Chang H, Santisteban MM, Racchumi G, Murphy M, Van Rooijen N, Anrather J, Iadecola C. Perivascular macrophages mediate the neurovascular and cognitive dysfunction associated with hypertension. J Clin Invest. 126:4674, 2016.

Garcia-Bonilla L, Faraco G, Moore J, Murphy M, Racchumi G, Srinivasan J, Brea D, Iadecola C, Anrather J. Spatio-temporal profile, phenotypic diversity, and fate of recruited monocytes into the post-ischemic brain. J Neuroinflammation. 13:285, 2016.

Benakis C, Brea D, Caballero S, Faraco G, Moore J, Murphy M, Sita G, Racchumi G, Ling L, Pamer EG, Iadecola C, Anrather J. Commensal microbiota affects ischemic stroke outcome by regulating intestinal γδ T cells. Nat Med. 22:516, 2016.

Faraco G, Park L, Zhou P, Lou W, Paul SM, Anrather J, Iadecola C. Hypertension enhances Aβ-induced neurovascular dysfunction, promotes β-secretase activity and leads to amyloidogenic processing of APP. J Cereb Blood Flow Metab. 36:241, 2016.

Faraco G, Iadecola C. Hypertension: A Harbinger of Stroke and Dementia. Hypertension. 62:810, 2013

Faraco G, Moraga A, Moore J, Anrather J, Pickel VM, Iadecola C. Circulating Endothelin-1 Alters Critical Mechanisms Regulating Cerebral Microcirculation. Hypertension. 62:759, 2013.

Capone C, Faraco G, Peterson JR, Coleman C, AnratherJ, Milner TA, Pickel VM, Davisson RL, and Iadecola C: Central Cardiovascular Circuits Contribute to the Neurovascular Dysfunction in Angiotensin II Hypertension. The Journal of Neuroscience 32:4878, 2012.

Capone C, Faraco G, Park L, Cao X, Davisson RL, Iadecola C.: The cerebrovascular dysfunction induced by slow pressor doses of angiotensin-II precedes the development of hypertension. Am J Physiol Heart Circ Physiol. 300:H397, 2011.

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