Abstract
The biological activities of interleukins, a group of circulating cytokines, are linked to the immuno-pathways involved in many diseases. Mounting evidence suggests that interleukin-1β (IL-1β) plays a significant role in the pathogenesis of various types of hypertension. In this review, we summarized recent findings linking IL-1β to systemic arterial hypertension, pulmonary hypertension, and gestational hypertension. We also outlined the new progress in elucidating the potential mechanisms of IL-1β in hypertension, focusing on it’s regulation in inflammation, vascular smooth muscle cell function, and extracellular remodeling. In addition, we reviewed recent studies that highlight novel findings examining the function of non-coding RNAs in regulating the activity of IL-1β and its associated proteins in the setting of hypertension. The information collected in this review provides new insights into understanding the pathogenesis of hypertension and could lead to the discovery of new anti-hypertensive therapies to combat this highly prevalent disease.
Highlights
Hypertension, or high blood pressure, is a multifactorial disease related to genetic, environmental, demographic, lifestyle, vascular, and neuroendocrine disorders; and is a serious medical condition that can increase the risk of heart, brain, kidney, and other diseases, making it a major cause of premature death worldwide [1–6]
Recent reports showed that hypertension development and EMC changes were limited in SHR rats exposed to ischemic conditioning; this phenotype was accompanied by a marked decrease in IL-1β, implying the depressing effects on the extracellular matrix (ECM) was due to the lowered IL-1β [52]
It has been generally assumed that most genetic information is transacted by proteins via encoding mRNAs, recent evidence suggests that the majority of the genomes of mammals is transcribed into non-coding RNAs (ncRNAs) that does not encode a protein, including microRNAs, small interfering RNAs, PIWI-interacting RNAs and various classes of long ncRNAs
Summary
Over recent years IL-1β has been linked in various types of hypertension such as SAH, PH, and GH [8,9], highlighting the importance of this interleukin in the progression of hypertension. A few studies have found that patients with essential hypertension displayed high levels of IL-1β in their serum, indicating the pro-hypertensive effects of IL-1β [8,15] In line with these results, IL-1Ra, the inhibitor of the IL-1β receptor, was shown to be elevated in hypertension, which was considered to play a role in combating the IL-1β induced inflammation in hypertension [8,19]. Silencing macrophage-specific expression of MyD88, the molecular adaptor protein downstream of IL-1R1 stimulation, disrupted the progression of PH in mice, leading to the speculation that the IL-1R1/MyD88 interaction is vital for facilitating signaling events that lead to hypertension [26] In line with these studies, suppressing IL-1R1 with Anakinra has improved inflammation and cardiovascular outcomes in both human and animal models of PH [25,28,29].
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