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Recent findings suggest that miR-145 may be protective against thrombosis.

MicroRNAs (miRs) are small non-coding RNAs that downregulate gene expression. Interestingly, miR-145 has been reported to downregulate the expression of important factors in the coagulation system (tissue factor and factor XI) in vitro. Furthermore, miR-145 has be shown to decrease venous thrombus formation in a mouse model.

In a recent paper, published in Blood, we investigated the association between plasma levels of miR-145 and risk of future VTE. We found that plasma levels of miR-145 were inversely associated with VTE risk. Participants with miR-145 levels in the highest quartile had a 49% lower risk of VTE compared with those with miR-145 in the lowest quartile, and this association remained after adjustment for several potential confounders. Our observation of a protective role of miR-145 for VTE, implies that miR-145 could be a potential target for VTE prevention in the future.

Link to the publication:

Morelli et al. High microRNA-145 plasma levels are associated with decreased risk of future incident venous thromboembolism - The HUNT study.

In a recent study, we showed that 1/4 of all venous thromboembolism (VTE) events in the population can be attributed to overweight and obesity.  

Obesity has emerged as one of the most relevant modifiable risk factors for venous thromboembolism (VTE) over the past decades. Obesity is associated with a two- to three-fold increased risk of VTE, and the risk increases linearly with increasing body mass index (BMI). However, data on the proportion of incident VTEs attributed to overweight and obesity in the general population are limited. We therefore investigated the population attributable fraction of overweight and obesity for VTE using data from the 4-7 surveys of the Tromsø study. More than 36 000 people were included in the study and followed for a median of 14 years.

We found that almost 25% of all VTEs in the population could be attributed to overweight and obesity. Thus, from a public health perspective, overweight and obesity are major contributors to the VTE burden in the general population. Our findings further suggest that public health efforts to lower the prevalence of obesity along with targeted interventions to reduce thrombosis risk in overweight and obese individuals may substantially lower the incidence of VTE in the general population.

The paper was published online in Thrombosis and Haemostasis in August 2023, and it also received an accompanying editorial commentary.

You can find the original paper here:

Frischmuth et al. The Risk of Incident Venous Thromboembolism Attributed to Overweight and Obesity: The Tromsø Study. Thromb Haemost 2023 Aug 7. doi: 10.1055/s-0043-1772212.

Editorial commentary:

Martin et al. Venous Thromboembolism and Obesity: Moving Toward a Better Understanding of the Population-Attributable Risk. Thromb Haemost. 2023 Oct 9. doi: 10.1055/s-0043-1776010.

Obesity is a risk factor for VTE. Illustration: MostPhotos.com

High levels of coagulation factor VIII (FVIII) and large platelets (reflected by a high mean platelet volume [MPV]), are separately associated with increased risk of venous thromboembolism (VTE). Whether the combination of the two yields excessive VTE risk has not been studied. We therefore assessed the combined effects of MPV and FVIII on risk of VTE in a nested case-control study. We found that individuals with high MPV and high FVIII (highest tertiles) had a 2.7-fold higher risk of VTE compared to those with low levels of both factors (lowest tertiles). In those with the combined exposure, 52% of the VTE could be attributed to the biological interaction between MPV and FVIII. These findings support that large platelets could play a role for the mechanism by which high FVIII increases VTE risk.

 You can find the original paper here:

Hansen et al. Combined effect of high factor VIII levels and high mean platelet volume on the risk of future incident venous thromboembolism. J Thromb Haemost. 2023 Oct;21(10):2844-2853. doi: 10.1016/j.jtha.2023.06.022.

Weak hand grip strenght was associated with increased risk of recurrence after a first venous thromboembolism.

There is limited knowledge about the relationship between muscle strength and risk of recurrence and mortality after a first event of venous thromboembolism (VTE). We investigated the relationship between hand grip strength and mortality in 545 participants with a first VTE recruited from the Tromsø study. We found that a weak hand grip strength was associated with a 2-fold increased risk of recurrent VTE and a 34% increased risk of death.

To read more about our findings, please follow this link:

Leknessund et al. Hand grip strength in venous thromboembolism: risk of recurrence and mortality. Res Pract Thromb Haemost. 2023 Jun 29;7(5):102138. doi: 10.1016/j.rpth.2023.102138.

C1-inhibitor is an important inhibitor of the complement system. This protein is also known to inhibit several proteases involved in the coagulation system. In a newly published study, we investigated the association between plasma levels of C1-inhibitor and risk of venous thromboembolism (VTE). In addition, we investigated the effect of C1-inhibitor on thrombin generation ex vivo. We found that individuals with high levels of C1 inhibitor (highest quartile) had a 32% lower risk of VTE. We also showed that C1 inhibitor inhibited thrombin generation initiated by the intrinsic coagulation pathway.

You can find the original paper here:

Grover et al. High plasma levels of C1-inhibitor are associated with lower risk of future venous thromboembolism. J Thromb Haemost. 2023;21:1849-1860. doi: 10.1016/j.jtha.2023.03.024.

K.G. Jebsen Thrombosis Research and Expertise Center (K.G. Jebsen TREC) was supported by an independent research grant from Stiftelsen Kristian Gerhard Jebsen in the period 2014-2020.

You can read more about our activities in this period on the K.G. Jebsen TREC blog available at https://site.uit.no/trec/.

We aim to reduce the suffering and burden of venous thrombosis through excellent and world leading research.

The total suffering and health burden caused by venous thrombosis (VTE) is tremendous. In Norway, one person suffers from VTE every hour and every forth hour one person dies from a VTE-realated cause.

Up to half of the patients who get VTE in their legs are subsequently afflicted with pain and swelling due to reduced circulation. Further, the socioeconomic burden related to treatment of the disease and loss of income due to work-related disability is very high.

Our research

VTE is a common disease with unclear and complicated disease development for which few risk factors are known.

Previous research has revealed some risk factors that can lead to VTE. Still, several factors have not yet been identified, and there is insufficient knowledge about how the known risk factors work together.

In TREC, we combine laboratory research, patient-oriented research and population-based research to reveal new risk factors and mechanisms for the formation of VTE, which in turn can contribute to improved prevention and tailored treatment of the disease.

Health studies such as the as the Tromsø study, the HUNT study (Helseundersøkelsen i Nord-Trøndelag) are the cornerstones of our research.

Organization

TREC is a translational research group led by Professor John-Bjarne Hansen.

TREC is a part of the Department of Clinical Medicine at the Faculty of Health Sciences. The group's research activity take place across several disciplines such as medical biology, clinical medicine and community medicine.

TREC also cooperates closely with research environments at other universities and hospitals in Norway and internationally.

TREC was funded by Stiftelsen K. G. Jebsen from 2014-2020 as the first and so far only K. G. Jebsen Center for Medical Research established in Northern Norway.

Thrombosis occurs when a blood clot forms on the inside of a blood vessel, obstructing the flow of blood through the circulatory system.

While arterial blood clots cause heart attacks and strokes, blood clots may also form in the slow-flowing venous system.

Veins are blood vessels that carry blood back to the lungs and heart from the body’s different organs. A deep vein thrombosis is a blood clot formed in a deep vein, usually in the leg, thigh and/or pelvis.

When blood flow through a vein is obstructed by a blood clot, the increased venous pressure below the clot causes swelling and pain in the affected limb.

A part of the blood clot may also break off and travel with the blood stream until it lodges in the lung vessels. This is called pulmonary embolism, and may result in shortness of breath, chest pain, heart failure and death.

Collectively, deep vein thrombosis and pulmonary embolism are called venous thromboembolism (VTE).