What is the clinical evidence from this study?

Study design: Other. Population: Angiotensin II-induced hypertension and ventricular remodeling. Intervention: Etanercept vs. Vehicle (Saline). Primary outcome: Mean arterial pressure (mmHg) (p=<0.05).

What question did this study set out to answer?

To investigate the molecular signaling pathways and the role of oxidative stress in tumor necrosis factor-alpha (TNF-α)-mediated adverse ventricular remodeling during angiotensin II (Ang II) infusion.

September 17, 2015Civil War Book ReviewOpen Access

Tumor Necrosis Factor - Alpha Is Essential for Angiotensin II-Induced Ventricular Remodeling: Role for Oxidative Stress

Q: What are the key findings of this study?

Etanercept treatment significantly blunted Angiotensin II-induced hypertension (133 vs 154 mmHg) and cardiac hypertrophy in wild-type mice.

Q: What question did this study set out to answer?

To investigate the molecular signaling pathways and the role of oxidative stress in tumor necrosis factor-alpha (TNF-α)-mediated adverse ventricular remodeling during angiotensin II (Ang II) infusion.

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Key result

Etanercept blunts Angiotensin II-induced hypertension by ~21 mmHg and limits cardiac hypertrophy in mice.

P<0.05

Why the study?

Does TNF-α inhibition prevent Angiotensin II-induced hypertension and adverse cardiac remodeling in mice?

Population

Male, 8-10 week-old, wild-type (WT) and TNF-α knockout (TNF-α-/-) mice

Comparison

TNF-α inhibition via genetic knockout or… vs Wild-type mice receiving Angiotensin II infusion…

Design

Preclinical

Follow-up

14 days

Authors

SSSrinivas SriramulaUniversidade Federal de Minas Gerais JFJoseph FrancisPennington Biomedical Research Center

Discussion

Member takes

Implication

Supports TNF-α role in experimental Ang II effects; hypothesis-generating and should not change clinical practice.

Key Points

To investigate the molecular signaling pathways and the role of oxidative stress in tumor necrosis factor-alpha (TNF-α)-mediated adverse ventricular remodeling during angiotensin II (Ang II) infusion.
Infused wild-type and TNF-α knockout (TNF-α-/-) mice with Ang II at 1 μg/kg/min continuously for 14 days.
Treated a cohort of wild-type mice with the TNF-α inhibitor etanercept (8 mg/kg every 3 days) for 2 weeks during Ang II infusion.
Evaluated blood pressure, cardiac hypertrophy (heart weight-to-body weight ratio), myocardial fibrosis, reactive oxygen species, NADPH oxidase subunits, and MAPK/NF-κB pathway activation.
Ang II infusion induced significant myocardial perivascular and interstitial fibrosis alongside collagen I, collagen III, CTGF, and TGF-β upregulation in wild-type mice, but these alterations were attenuated in TNF-α-/- mice.
Ang II-induced reactive oxygen species formation and NADPH oxidase subunit upregulation were present in wild-type mice but absent in TNF-α-/- mice.
Etanercept treatment significantly blunted Ang II-induced hypertension (133 ± 4 vs 154 ± 3 mmHg, p < 0.05) and cardiac hypertrophy (heart weight to body weight ratio: 4.8 ± 0.2 vs 5.6 ± 0.3, p < 0.05) while suppressing NF-κB, p38 MAPK, and JNK activation.

Structured PICO

Does TNF-α inhibition prevent Angiotensin II-induced hypertension and adverse cardiac remodeling in mice?

Population

Male, 8-10 week-old, wild-type (WT) and TNF-α knockout (TNF-α-/-) mice

Intervention

TNF-α inhibition via genetic knockout (TNF-α-/-) or pharmacological blockade (etanercept 8 mg/kg intraperitoneally every 3 days) during chronic Angiotensin II infusion (1 μg/kg/min for 14 days)

Comparator

Wild-type mice receiving Angiotensin II infusion without TNF-α inhibition, and mice receiving saline infusion

Outcome

Ventricular remodeling (cardiac fibrosis, hypertrophy) and hypertensionsurrogate

Main Result

Absolute Event Rate: 133% vs 154%

p-value: p=<0.05

TNF-α is essential for Angiotensin II-induced hypertension and adverse cardiac remodeling, with its effects mediated through oxidative stress and the MAPK/TGF-β/NF-κB pathway.

Cite This Study

Sriramula et al. (2015) studied Angiotensin II-induced hypertension and ventricular remodeling. Etanercept vs. Vehicle (Saline) was evaluated on Mean arterial pressure (mmHg) (p=<0.05). Etanercept treatment significantly blunted Angiotensin II-induced hypertension (133 vs 154 mmHg) and cardiac hypertrophy in wild-type mice.

synapsesocial.com/papers/6a0ecf60a14f152feaf9dee1 https://doi.org/10.1371/journal.pone.0138372

Topics

Hypertension management

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Tumor Necrosis Factor - Alpha Is Essential for Angiotensin II-Induced Ventricular Remodeling: Role for Oxidative Stress

Discussion

Member takes

Implication

Key Points

Structured PICO

Main Result

Cite This Study

Topics

Tumor Necrosis Factor - Alpha Is Essential for Angiotensin II-Induced Ventricular Remodeling: Role for Oxidative Stress

Discussion

Member takes

Implication

Key Points

Structured PICO

Main Result

Cite This Study

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Topics

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