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Novel Immune Mechanisms in Hypertension and Cardiovascular Risk
Ryszard Nosalski1,2, Eilidh McGinnigle1, Mateusz Siedlinski2
1BHF Centre for Excellence Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, Scotland UK.
Insights
Inflammation and immune responses are key drivers of hypertension and cardiovascular risk. Targeting these mechanisms, not just blood pressure, is crucial for effective treatment and risk reduction.
Area of Science:
- Cardiovascular Research
- Immunology
- Nephrology
Background:
- Hypertension significantly elevates cardiovascular risk, with underlying mechanisms incompletely understood.
- Current treatments for hypertension are often insufficient to mitigate associated cardiovascular risks.
- Inflammatory pathways are increasingly recognized as a critical link between hypertension and cardiovascular disease.
Purpose of the Study:
- To review emerging immune and inflammatory mechanisms implicated in hypertension.
- To explore the therapeutic potential of targeting these newly identified pathways.
Main Methods:
- Review of experimental models and genome-wide association studies (GWAS).
- Analysis of immune cell infiltration and mediator roles in hypertension.
- Investigation of specific immune genes, chemokines, and microRNAs.
Main Results:
- Low-grade inflammation contributes to hypertension, with the SH2B3 immune gene identified as a key driver.
- Oxidative stress generates neoantigens that modulate immune responses via chemokines (e.g., RANTES, IP-10) and microRNAs (e.g., miR-21, miR-155).
- Innate and adaptive immune cells infiltrate vasculature and kidneys, releasing pro-inflammatory mediators and reactive oxygen species, thereby impairing function.
Conclusions:
- Immune and inflammatory mechanisms are integral to the hypertension-cardiovascular risk relationship.
- Reducing blood pressure alone is insufficient; addressing these underlying immune and inflammatory pathways is essential for comprehensive risk reduction.
Purpose Of Review:
Hypertension is a common disorder with substantial impact on public health due to highly elevated cardiovascular risk. The mechanisms still remain unclear and treatments are not sufficient to reduce risk in majority of patients. Inflammatory mechanisms may provide an important mechanism linking hypertension and cardiovascular risk. We aim to review newly identified immune and inflammatory mechanisms of hypertension with focus on their potential therapeutic impact.
Recent Findings:
In addition to the established role of the vasculature, kidneys and central nervous system in pathogenesis of hypertension, low-grade inflammation contributes to this disorder as indicated by experimental models and GWAS studies pointing to SH2B3 immune gene as top key driver of hypertension. Immune responses in hypertension are greatly driven by neoantigens generated by oxidative stress and modulated by chemokines such as RANTES, IP-10 and microRNAs including miR-21 and miR-155 with other molecules under investigation. Cells of both innate and adoptive immune system infiltrate vasculature and kidneys, affecting their function by releasing pro-inflammatory mediators and reactive oxygen species.
Summary:
Immune and inflammatory mechanisms of hypertension provide a link between high blood pressure and increased cardiovascular risk, and reduction of blood pressure without attention to these underlying mechanisms is not sufficient to reduce risk.