Structural Remodeling of Sympathetic Innervation in Atherosclerotic Blood Vessels: Role of Atherosclerotic Disease Progression and Chronic Social Stress

Research output: Contribution to journalArticle

Abstract

OBJECTIVE: The sympathetic nervous system (SNS) can undergo dramatic structural plasticity in response to behavioral factors and/or the presence of disease, leading to SNS hyperinnervation of peripheral tissues. The SNS has been proposed as an important mediator between stressful behavior and the progression of atherosclerosis in the vasculature. The present study examined whether structural remodeling of the SNS occurs in the vasculature in a genetically hyperlipidemic animal model of atherosclerosis, the Watanabe heritable hyperlipidemic rabbit (WHHL; relative to normolipidemic New Zealand white rabbits [NZW]), and whether SNS plasticity is driven by the progression of disease and/or by stressful social behavior. METHODS: WHHL and NZW rabbits were assigned to an unstable or stable social environment for 4 months. Aortic atherosclerosis was assessed and SNS aortic innervation quantified using immunofluorescent microscopy. RESULTS: Numerous SNS varicosities were observed throughout the aorta in WHHLs and NZWs, extending into the vascular media and intima, an innervation pattern not previously reported. WHHLs exhibited significantly greater innervation than NZWs (F(1,41) = 55.3, p < .001), with extensive innervation of the atherosclerotic neointima. The innervation density was highly correlated with the extent of disease in the WHHLs (r(21) = 0.855, p < .001). Social environment did not influence innervation in NZWs (aortic arch: p = .078, thoracic aorta: p = .34) or WHHLs (arch: p = .97, thoracic: p = .61). CONCLUSIONS: The findings suggest that hyperinnervation is driven largely by the progression of disease rather than social environment. SNS innervation patterns observed in atherosclerotic human and mouse aortas were consistent with the rabbit, suggesting that SNS hyperinnervation of the diseased vessel wall is a general feature across mammalian species.

Original languageEnglish (US)
JournalPsychosomatic Medicine
DOIs
StateAccepted/In press - Jun 29 2016

Fingerprint

Sympathetic Nervous System
Blood Vessels
Disease Progression
Social Environment
Rabbits
Atherosclerosis
Thoracic Aorta
Aorta
Autonomic Nervous System Diseases
Tunica Intima
Tunica Media
Neointima
Progression
Nervous System
Vessel
Blood
Social Behavior
Microscopy
Thorax
Animal Models

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Applied Psychology
  • Arts and Humanities (miscellaneous)
  • Developmental and Educational Psychology

Cite this

@article{c57a2b0b41914f6bb159fe3e3f7af64f,
title = "Structural Remodeling of Sympathetic Innervation in Atherosclerotic Blood Vessels: Role of Atherosclerotic Disease Progression and Chronic Social Stress",
abstract = "OBJECTIVE: The sympathetic nervous system (SNS) can undergo dramatic structural plasticity in response to behavioral factors and/or the presence of disease, leading to SNS hyperinnervation of peripheral tissues. The SNS has been proposed as an important mediator between stressful behavior and the progression of atherosclerosis in the vasculature. The present study examined whether structural remodeling of the SNS occurs in the vasculature in a genetically hyperlipidemic animal model of atherosclerosis, the Watanabe heritable hyperlipidemic rabbit (WHHL; relative to normolipidemic New Zealand white rabbits [NZW]), and whether SNS plasticity is driven by the progression of disease and/or by stressful social behavior. METHODS: WHHL and NZW rabbits were assigned to an unstable or stable social environment for 4 months. Aortic atherosclerosis was assessed and SNS aortic innervation quantified using immunofluorescent microscopy. RESULTS: Numerous SNS varicosities were observed throughout the aorta in WHHLs and NZWs, extending into the vascular media and intima, an innervation pattern not previously reported. WHHLs exhibited significantly greater innervation than NZWs (F(1,41) = 55.3, p < .001), with extensive innervation of the atherosclerotic neointima. The innervation density was highly correlated with the extent of disease in the WHHLs (r(21) = 0.855, p < .001). Social environment did not influence innervation in NZWs (aortic arch: p = .078, thoracic aorta: p = .34) or WHHLs (arch: p = .97, thoracic: p = .61). CONCLUSIONS: The findings suggest that hyperinnervation is driven largely by the progression of disease rather than social environment. SNS innervation patterns observed in atherosclerotic human and mouse aortas were consistent with the rabbit, suggesting that SNS hyperinnervation of the diseased vessel wall is a general feature across mammalian species.",
author = "Noller, {Crystal M.} and Mendez, {Armando J} and Angela Szeto and Marcia Boulina and Maria Llabre and Julia Zaias and Neil Schneiderman and Philip McCabe",
year = "2016",
month = "6",
day = "29",
doi = "10.1097/PSY.0000000000000360",
language = "English (US)",
journal = "Psychosomatic Medicine",
issn = "0033-3174",
publisher = "Lippincott Williams and Wilkins",

}

TY - JOUR

T1 - Structural Remodeling of Sympathetic Innervation in Atherosclerotic Blood Vessels

T2 - Role of Atherosclerotic Disease Progression and Chronic Social Stress

AU - Noller, Crystal M.

AU - Mendez, Armando J

AU - Szeto, Angela

AU - Boulina, Marcia

AU - Llabre, Maria

AU - Zaias, Julia

AU - Schneiderman, Neil

AU - McCabe, Philip

PY - 2016/6/29

Y1 - 2016/6/29

N2 - OBJECTIVE: The sympathetic nervous system (SNS) can undergo dramatic structural plasticity in response to behavioral factors and/or the presence of disease, leading to SNS hyperinnervation of peripheral tissues. The SNS has been proposed as an important mediator between stressful behavior and the progression of atherosclerosis in the vasculature. The present study examined whether structural remodeling of the SNS occurs in the vasculature in a genetically hyperlipidemic animal model of atherosclerosis, the Watanabe heritable hyperlipidemic rabbit (WHHL; relative to normolipidemic New Zealand white rabbits [NZW]), and whether SNS plasticity is driven by the progression of disease and/or by stressful social behavior. METHODS: WHHL and NZW rabbits were assigned to an unstable or stable social environment for 4 months. Aortic atherosclerosis was assessed and SNS aortic innervation quantified using immunofluorescent microscopy. RESULTS: Numerous SNS varicosities were observed throughout the aorta in WHHLs and NZWs, extending into the vascular media and intima, an innervation pattern not previously reported. WHHLs exhibited significantly greater innervation than NZWs (F(1,41) = 55.3, p < .001), with extensive innervation of the atherosclerotic neointima. The innervation density was highly correlated with the extent of disease in the WHHLs (r(21) = 0.855, p < .001). Social environment did not influence innervation in NZWs (aortic arch: p = .078, thoracic aorta: p = .34) or WHHLs (arch: p = .97, thoracic: p = .61). CONCLUSIONS: The findings suggest that hyperinnervation is driven largely by the progression of disease rather than social environment. SNS innervation patterns observed in atherosclerotic human and mouse aortas were consistent with the rabbit, suggesting that SNS hyperinnervation of the diseased vessel wall is a general feature across mammalian species.

AB - OBJECTIVE: The sympathetic nervous system (SNS) can undergo dramatic structural plasticity in response to behavioral factors and/or the presence of disease, leading to SNS hyperinnervation of peripheral tissues. The SNS has been proposed as an important mediator between stressful behavior and the progression of atherosclerosis in the vasculature. The present study examined whether structural remodeling of the SNS occurs in the vasculature in a genetically hyperlipidemic animal model of atherosclerosis, the Watanabe heritable hyperlipidemic rabbit (WHHL; relative to normolipidemic New Zealand white rabbits [NZW]), and whether SNS plasticity is driven by the progression of disease and/or by stressful social behavior. METHODS: WHHL and NZW rabbits were assigned to an unstable or stable social environment for 4 months. Aortic atherosclerosis was assessed and SNS aortic innervation quantified using immunofluorescent microscopy. RESULTS: Numerous SNS varicosities were observed throughout the aorta in WHHLs and NZWs, extending into the vascular media and intima, an innervation pattern not previously reported. WHHLs exhibited significantly greater innervation than NZWs (F(1,41) = 55.3, p < .001), with extensive innervation of the atherosclerotic neointima. The innervation density was highly correlated with the extent of disease in the WHHLs (r(21) = 0.855, p < .001). Social environment did not influence innervation in NZWs (aortic arch: p = .078, thoracic aorta: p = .34) or WHHLs (arch: p = .97, thoracic: p = .61). CONCLUSIONS: The findings suggest that hyperinnervation is driven largely by the progression of disease rather than social environment. SNS innervation patterns observed in atherosclerotic human and mouse aortas were consistent with the rabbit, suggesting that SNS hyperinnervation of the diseased vessel wall is a general feature across mammalian species.

UR - http://www.scopus.com/inward/record.url?scp=84976591462&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84976591462&partnerID=8YFLogxK

U2 - 10.1097/PSY.0000000000000360

DO - 10.1097/PSY.0000000000000360

M3 - Article

C2 - 27359178

AN - SCOPUS:84976591462

JO - Psychosomatic Medicine

JF - Psychosomatic Medicine

SN - 0033-3174

ER -