CERIC Center of Excellence for Research on Inflammation and Cardiovascular disease

CERIC is a Linné Center supported by the Swedish Research Council (Vetenskapsrådet)

Next CERIC Seminar

Friday February 19th CMM Lecture Hall (L8:00)


Speaker: Enikö Sonkoly, Department of Medicine, Karolinska Institute
Title: MircoRNA 146a - a suppressor of IL17 mediated inflammation
Host: Mona Ståhle

ERC grant for Lars Maegdefessel

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Therapeutic and Biomarker Potential of long non-coding RNAs in Vascular Disease

Acronym: NORVAS

Abstract
The contribution of cardiovascular disease to human morbidity and mortality continues to steadily increase in our aging European society. In response, extraordinary efforts have been launched to determine the molecular and pathophysiological characteristics of its etiology.
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    The contribution of cardiovascular disease to human morbidity and mortality continues to steadily increase in our aging European society. In response, extraordinary efforts have been launched to determine the molecular and pathophysiological characteristics of its etiology. The collective work of multiple research groups has uncovered a complex transcriptional and post-transcriptional regulatory milieu, which is believed to be essential for maintaining cardiovascular homeostasis. Recently, non-coding RNAs, especially the ones with antisense capabilities such as microRNAs or ‘natural antisense transcripts’ (NATs) have received much attention. They have been identified as important transcriptional and post-transcriptional inhibitors of gene expression.
    This current proposal describes the development of novel diagnostic and therapeutic strategies to limit the burden of cardiovascular disease in general, and abdominal aortic aneurysms as well as carotid stenosis and subsequent stroke in particular. Using transcriptomic-profiling techniques on human diseased tissue samples, we have identified several NATs as novel crucial regulators of smooth muscle cell survival via targeting distinct growth factors, as well as tumor suppressor and cell cycle regulatory genes in the vascular system. We are using disease relevant experimental in vivo models (rodents and LDLR-/- mini-pigs) to functionally assess how inhibition of these two NATs influences aneurysm progression and atherosclerotic plaque vulnerability. One focus of our studies is to utilize local delivery mechanisms for non-coding RNA modulators, such as drug eluting balloons and stents, to enhance the translational feasibility of our findings. Furthermore, we have access to unique human plasma material from patients with early and advanced forms of aneurysm disease, enabling us to investigate the biomarker value of non-coding RNAs in recognizing patients with acutely ruptured aneurysms, as well as predicting the future risk of rupture.
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CERIC's goal is to be an internationally leading center in chronic inflammation, the pathological process that links inflammatory disorders such as multiple sclerosis, rheumatoid arthritis and psoriasis with atherosclerotic cardiovascular disease. For this purpose, we will build on existing, strong research in inflammatory mediators, autoimmunity , chronic inflammatory diseases, and cardiovascular disease at the Karolinska Institutet.

The following research aims will be addressed:



Aim 1: To determine why chronic inflammation sometimes, but not always, results in increased atherosclerosis and leads to myocardial infarction or stroke (cardiovascular disease).

Aim 2: To identify novel therapy targets and investigate the effects of targeted therapies against chronic inflammatory diseases and cardiovascualr diseases

Taken together, these two approaches will allow us to both understand the etiology and pathogenesis of chronic inflammatory diseases and cardiovascular disease and provide a basis for improved prevention and therapy for chronic inflammatory diseases and inflammatory cardiovascular disease, two major challenges to health in the population.

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