Acute Chikungunya Infection Induces Vascular Dysfunction by Directly Disrupting Redox Signaling in Endothelial Cells

Area of Science:

• Cardiovascular Research
• Infectious Diseases
• Vascular Biology

Background:

• Chikungunya virus (CHIKV) infection causes febrile illness, joint pain, and cardiovascular complications.
• CHIKV infection is associated with reactive oxygen species (ROS) and cytokine release, potentially disrupting vascular homeostasis.
• The precise mechanisms by which CHIKV impacts vascular function remain incompletely understood.

Purpose of the Study:

• To investigate the hypothesis that CHIKV induces arterial dysfunction by directly impacting redox-related mechanisms in vascular cells.
• To elucidate the role of inducible nitric oxide synthase (iNOS) in CHIKV-induced vascular dysfunction.
• To examine the effects of CHIKV infection on vascular ROS production and signaling pathways.

Main Methods:

• In vivo studies using wild-type and iNOS knockout mice infected with CHIKV or mock vehicle.
• Vascular function assessed using wire myography, blood pressure measurements, and biochemical assays for cytokines, ROS, and nitric oxide.
• In vitro studies involving CHIKV-infected endothelial cells to analyze protein expression.

Main Results:

• CHIKV infection induced significant vascular dysfunction, decreased systolic blood pressure, and altered cytokine profiles (increased IL-6 and IFN-γ).
• A marked hyporesponsiveness to phenylephrine was observed, which was prevented by iNOS inhibition or deletion, and endothelium removal.
• CHIKV infection increased vascular superoxide anion and nitrite production, decreased hydrogen peroxide, and elevated TBARS levels, indicating oxidative stress.

Conclusions:

• CHIKV infection directly impacts vascular cells, leading to arterial dysfunction through alterations in redox-related mechanisms.
• The study highlights the critical role of the ROS/NF-kB/iNOS/NO signaling pathway in CHIKV-associated cardiovascular complications.
• These findings suggest that targeting these pathways may offer therapeutic strategies for managing cardiovascular events in Chikungunya patients.