The Future of Vascular Biology and Medicine

Kinlay, Scott; Michel, Thomas; Leopold, Jane A.

doi:10.1161/circulationaha.116.023513

Cited by 18 publications

(16 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Collectively, these results indicate that gut dysbiosis may be a causal factor in the development of vascular dysfunction, and suggest a potential role for bacterial-derived LPS in mediating these events. These results extend recent data linking gut dysbiosis to the development of other cardiovascular abnormalities, including atherosclerosis and hypertension (60), and lend further support to the notion that the gut microbiota represent a future therapeutic target for cardiovascular disease (30).…”

Section: Discussionsupporting

confidence: 85%

Suppression of gut dysbiosis reverses Western diet-induced vascular dysfunction

Battson

Lee

Jarrell

et al. 2018

American Journal of Physiology-Endocrinology and Metabolism

View full text Add to dashboard Cite

Vascular dysfunction represents a critical preclinical step in the development of cardiovascular disease. We examined the role of the gut microbiota in the development of obesity-related vascular dysfunction. Male C57BL/6J mice were fed either a standard diet (SD) ( n = 12) or Western diet (WD) ( n = 24) for 5 mo, after which time WD mice were randomized to receive either unsupplemented drinking water or water containing a broad-spectrum antibiotic cocktail (WD + Abx) ( n = 12/group) for 2 mo. Seven months of WD caused gut dysbiosis, increased arterial stiffness (SD 412.0 ± 6.0 vs. WD 458.3 ± 9.0 cm/s, P < 0.05) and endothelial dysfunction (28% decrease in max dilation, P < 0.05), and reduced l-NAME-inhibited dilation. Vascular dysfunction was accompanied by significant increases in circulating LPS-binding protein (LBP) (SD 5.26 ± 0.23 vs. WD 11 ± 0.86 µg/ml, P < 0.05) and interleukin-6 (IL-6) (SD 3.27 ± 0.25 vs. WD 7.09 ± 1.07 pg/ml, P < 0.05); aortic expression of phosphorylated nuclear factor-κB (p-NF-κB) ( P < 0.05); and perivascular adipose expression of NADPH oxidase subunit p67phox ( P < 0.05). Impairments in vascular function correlated with reductions in Bifidobacterium spp. Antibiotic treatment successfully abrogated the gut microbiota and reversed WD-induced arterial stiffness and endothelial dysfunction. These improvements were accompanied by significant reductions in LBP, IL-6, p-NF-κB, and advanced glycation end products (AGEs), and were independent from changes in body weight and glucose tolerance. These results indicate that gut dysbiosis contributes to the development of WD-induced vascular dysfunction, and identify the gut microbiota as a novel therapeutic target for obesity-related vascular abnormalities.

show abstract

Section: Discussionsupporting

confidence: 85%

Suppression of gut dysbiosis reverses Western diet-induced vascular dysfunction

Battson

Lee

Jarrell

et al. 2018

American Journal of Physiology-Endocrinology and Metabolism

View full text Add to dashboard Cite

show abstract

“…104 In addition, the gut microbiota can affect the rate of progression of experimental atherosclerosis. 105, 106 Whether this or other microbiota affects intracranial atherosclerosis is unknown. Gut microbes can affect platelet responsiveness and clot formation, 107 important factors in hemostasis and thrombosis.…”

Section: Part I Cerebrovascular Disease: the Prelude To Strokementioning

confidence: 99%

Cerebral Vascular Disease and Neurovascular Injury in Ischemic Stroke

Silva

Chen

et al. 2017

Circulation Research

300

237

View full text Add to dashboard Cite

The consequences of cerebrovascular disease are among the leading health issues worldwide. Large and small cerebral vessel disease can trigger stroke and contribute to the vascular component of other forms of neurological dysfunction and degeneration. Both forms of vascular disease are driven by diverse risk factors, with hypertension as the leading contributor. Despite the importance of neurovascular disease and subsequent injury following ischemic events, fundamental knowledge in these areas lag behind our current understanding of neuroprotection and vascular biology in general. The goal of this review is to address select key structural and functional changes in the vasculature that promote hypoperfusion and ischemia, while also affecting the extent of injury and effectiveness of therapy. In addition, as damage to the blood-brain barrier (BBB) is one of the major consequences of ischemia, we discuss cellular and molecular mechanisms underlying ischemia-induced changes in BBB integrity and function, including alterations in endothelial cells and the contribution of pericytes, immune cells, and matrix metalloproteinases. Identification of cell types, pathways, and molecules that control vascular changes before and after ischemia may result in novel approaches to slow the progression of cerebrovascular disease and lessen both the frequency and impact of ischemic events.

show abstract

“…Other potential mechanisms include the role of antibiotics in promoting dysbiosis of the gut, skin, and respiratory tract, affecting the interactions between colonizing flora in maintaining health and promoting immunity; it is also possible that antibiotics and dysbiosis function as modulators of vascular development. 34,35 Although the full relationship between early neonatal antibiotic exposures and subsequent childhood health remains to be defined, current evidence suggests that such exposures do affect preterm infants. Physicians should consider the risk/benefit balance of initiating antibiotic therapy for risk of EOS as well as for continuing empirical antibiotic therapy in the absence of a culture-confirmed infection.…”

Section: Antibiotic Stewardship In Preterm Eos Managementmentioning

confidence: 99%

Management of Neonates Born at ≤34 6/7 Weeks’ Gestation With Suspected or Proven Early-Onset Bacterial Sepsis

et al. 2018

View full text Add to dashboard Cite

Early-onset sepsis (EOS) remains a serious and often fatal illness among infants born preterm, particularly among newborn infants of the lowest gestational age. Currently, most preterm infants with very low birth weight are treated empirically with antibiotics for risk of EOS, often for prolonged periods, in the absence of a culture-confirmed infection. Retrospective studies have revealed that antibiotic exposures after birth are associated with multiple subsequent poor outcomes among preterm infants, making the risk/benefit balance of these antibiotic treatments uncertain. Gestational age is the strongest single predictor of EOS, and the majority of preterm births occur in the setting of other factors associated with risk of EOS, making it difficult to apply risk stratification strategies to preterm infants. Laboratory tests alone have a poor predictive value in preterm EOS. Delivery characteristics of extremely preterm infants present an opportunity to identify those with a lower risk of EOS and may inform decisions to initiate or extend antibiotic therapies. Our purpose for this clinical report is to provide a summary of the current epidemiology of preterm neonatal sepsis and provide guidance for the development of evidence-based approaches to sepsis risk assessment among preterm newborn infants.

show abstract

The Future of Vascular Biology and Medicine

Cited by 18 publications

References 51 publications

Suppression of gut dysbiosis reverses Western diet-induced vascular dysfunction

Suppression of gut dysbiosis reverses Western diet-induced vascular dysfunction

Cerebral Vascular Disease and Neurovascular Injury in Ischemic Stroke

Management of Neonates Born at ≤34 6/7 Weeks’ Gestation With Suspected or Proven Early-Onset Bacterial Sepsis

Contact Info

Product

Resources

About