Surreal illustration of disrupted blood vessels showing resistin's impact on cardiovascular health.

Unlocking Cardiovascular Health: How Resistin Impacts Your Body

Soraya Malik in Health & Wellness November 2025 • 4 min read.

"New Research Reveals Resistin's Role in Blood Clotting and Endothelial Function"

Cardiovascular diseases remain the leading cause of death globally, highlighting the critical need to understand the underlying factors contributing to these conditions. Among the key players in cardiovascular health is the vascular endothelium, the inner lining of blood vessels. Endothelial cells maintain a delicate balance between pro-coagulant and anti-coagulant processes, as well as inflammatory responses. Dysfunction in these cells can disrupt this balance, leading to thrombosis and coagulation issues.

One of the protective mechanisms of endothelial cells is the formation of activated protein C (APC), a crucial regulator of blood coagulation. APC is formed through a complex involving thrombin, thrombomodulin, and endothelial protein C receptor (EPCR). This complex helps to deactivate coagulation cascade factors, preventing excessive clotting and maintaining vascular health. Disruptions in this process can have significant consequences, underscoring the importance of understanding the factors that influence APC formation.

Emerging research has focused on resistin, an adipocyte-secreted hormone associated with obesity and insulin resistance, and its potential impact on cardiovascular health. While murine resistin is primarily expressed by adipocytes, its human counterpart is found predominantly in peripheral blood mononuclear cells and macrophages. Studies have shown that resistin can increase vascular adhesion molecules and promote monolayer permeability in endothelial cells. Recent findings now reveal a new role for resistin in disturbing APC formation, shedding light on its broader implications for cardiovascular health.

Resistin's Impact on Protein C Activation and EPCR Suppression

Surreal illustration of disrupted blood vessels showing resistin's impact on cardiovascular health.

A recent study investigated the effects of resistin on thrombin-induced protein C activation in endothelial cells. The findings revealed that resistin suppresses this activation, indicating a potential disruption in the body's natural anticoagulant processes. Further analysis showed that resistin treatment leads to a reduction in EPCR expression, while thrombomodulin (TM) levels remain unaffected. This suggests that resistin specifically targets EPCR, a key component in the APC formation complex.

To understand the underlying mechanisms, researchers explored the role of SP1, a nuclear transcription factor, in resistin's effects on EPCR expression. The study demonstrated that resistin induces the expression of SP1, which in turn leads to the downregulation of EPCR. This intricate relationship highlights how resistin can indirectly influence APC formation by modulating SP1 activity and subsequently affecting EPCR levels. Both inhibition and silencing of SP1 protein abolishes abnormal APC generation induced by resistin, which further confirms the relationship.

Resistin suppresses thrombin-induced protein C activation.
Resistin reduces EPCR expression but does not affect thrombomodulin levels.
Resistin induces SP1 expression.
Increased SP1 expression downregulates EPCR.

These findings uncover a novel role for resistin in disturbing APC formation, which has significant implications for cardiovascular health. By suppressing EPCR expression through SP1 induction, resistin disrupts the delicate balance of blood coagulation, potentially increasing the risk of thrombosis and related cardiovascular events. This discovery provides new insights into the complex interplay between adipokines, endothelial function, and cardiovascular health.

Implications and Future Directions

The discovery of resistin's role in disturbing APC formation opens new avenues for understanding and addressing cardiovascular risks associated with obesity and insulin resistance. By identifying the SP1-EPCR pathway as a key mediator of resistin's effects, researchers can explore targeted interventions to restore proper endothelial function and prevent thrombotic events. Further studies are needed to fully elucidate the clinical implications of these findings and develop effective strategies to mitigate the adverse cardiovascular effects of resistin.

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This article is based on research published under:

DOI-LINK: 10.1016/j.biopha.2018.09.160, Alternate LINK

Title: Resistin Impairs Activation Of Protein C By Suppressing Epcr And Increasing Sp1 Expression

Subject: Pharmacology

Journal: Biomedicine & Pharmacotherapy

Publisher: Elsevier BV

Authors: Pei Zhang, Yu Liu, Jiangli Su, Jie Bai, Shikai Zhao, Shouguo Zhao

Published: 2019-01-01

Everything You Need To Know

How does resistin affect cardiovascular health?

Resistin, primarily secreted by adipocytes, impacts cardiovascular health by disturbing the formation of activated protein C (APC), a crucial regulator of blood coagulation. Specifically, resistin suppresses thrombin-induced protein C activation in endothelial cells, disrupting the body's natural anticoagulant processes. This effect is mediated by resistin reducing the expression of endothelial protein C receptor (EPCR), a key component in the APC formation complex, while thrombomodulin (TM) levels remain unaffected. This ultimately increases the risk of thrombosis and related cardiovascular events.

What is activated protein C (APC) and why is it important?

Activated protein C (APC) is a crucial regulator of blood coagulation, formed through a complex involving thrombin, thrombomodulin, and endothelial protein C receptor (EPCR). APC deactivates coagulation cascade factors, preventing excessive clotting and maintaining vascular health. Resistin has been found to disrupt APC formation by suppressing EPCR expression. Without adequate APC formation, the risk of thrombosis and other cardiovascular events increases, highlighting the importance of understanding factors like resistin that influence APC formation.

How does resistin influence SP1 and EPCR expression, and what is the consequence?

The research indicates that resistin induces the expression of SP1, a nuclear transcription factor. Increased SP1 expression then leads to the downregulation of endothelial protein C receptor (EPCR). Since EPCR is essential for the formation of activated protein C (APC), this downregulation disrupts the delicate balance of blood coagulation. This intricate relationship highlights how resistin can indirectly influence APC formation by modulating SP1 activity and subsequently affecting EPCR levels.

What aspects of cardiovascular health related to resistin are not covered and require further research?

While this research sheds light on resistin's role in disturbing activated protein C (APC) formation and its impact on cardiovascular health, it primarily focuses on the mechanisms involving endothelial cells and the SP1-EPCR pathway. Further research is needed to fully understand the clinical implications of these findings. Specifically, future studies could explore potential interventions to restore proper endothelial function and prevent thrombotic events in individuals with elevated resistin levels. Additionally, investigating the interplay between resistin and other cardiovascular risk factors could provide a more comprehensive understanding of its impact.

What are the potential therapeutic implications of understanding resistin's impact on APC formation and the SP1-EPCR pathway?

The discovery that resistin disturbs activated protein C (APC) formation by suppressing endothelial protein C receptor (EPCR) expression, mediated through SP1, opens new avenues for understanding and addressing cardiovascular risks, particularly in individuals with obesity and insulin resistance. By identifying the SP1-EPCR pathway as a key mediator, researchers can explore targeted interventions to restore proper endothelial function and prevent thrombotic events. Future treatments may focus on modulating SP1 activity or directly targeting EPCR expression to mitigate the adverse cardiovascular effects of resistin.