Illustration of a heart with hyaluronan molecules representing heart inflammation and healing.

Decoding Hyaluronan: How This Natural Molecule Impacts Heart Health

Author's portrait.
Nico Varela in Health & Wellness June 2025 • 5 min read.

"Discover the surprising role of hyaluronan in heart inflammation and potential new therapeutic targets for NSTEMI patients."


Heart disease remains a leading cause of mortality worldwide, prompting ongoing research into the intricate mechanisms that contribute to its development and progression. Among the molecules attracting increasing attention is hyaluronan (HA), a naturally occurring substance found throughout the body, particularly in the extracellular matrix. While HA has long been recognized for its roles in skin health and joint lubrication, emerging evidence suggests it plays a significant, yet complex, role in cardiovascular health, especially in the context of acute coronary syndromes.

Acute coronary syndromes (ACS), such as Non-ST Elevation Myocardial Infarction (NSTEMI), are characterized by sudden reductions in blood flow to the heart, often due to plaque rupture and subsequent blood clot formation in the coronary arteries. This triggers an inflammatory response that can further damage the heart tissue. Understanding the precise molecular players involved in this inflammatory cascade is crucial for developing targeted therapies that can limit damage and improve patient outcomes.

Recent studies have begun to unravel the complex relationship between HA and heart inflammation. Of particular interest is the observation that HA exists in different molecular sizes, each with potentially distinct biological activities. High molecular weight HA (HMW-HA) is generally considered to have anti-inflammatory properties, while low molecular weight HA (LMW-HA) can paradoxically promote inflammation. This distinction is critical for understanding how HA contributes to the inflammatory processes in conditions like NSTEMI.

Hyaluronan's Inflammatory Role in NSTEMI: What the Research Shows

Illustration of a heart with hyaluronan molecules representing heart inflammation and healing.

A groundbreaking study aimed to investigate the specific role of HA in patients with NSTEMI by evaluating the expression of CD31, a marker found on monocytes (a type of white blood cell involved in inflammation). Researchers examined CD31 expression under both basal conditions and after stimulation with different sizes of HA – HMW-HA and LMW-HA – using E. Coli-LPS as a positive control to induce inflammation. The study included 20 healthy control subjects, 20 patients with stable angina, and 20 patients with NSTEMI.

Peripheral blood mononuclear cells (PBMCs) were isolated from all participants and stimulated with HMW-HA, LMW-HA, and E. Coli-LPS for 16 hours. The researchers then assessed CD31 protein expression on CD14+CD16- monocytes using flow cytometry, a technique that allows for the quantification of specific proteins on individual cells. This meticulous approach allowed them to pinpoint how different forms of HA affected the inflammatory response in different patient groups.

  • Basal Conditions: Under normal, unstimulated conditions, CD31 expression on monocytes did not significantly differ between the healthy control group, stable angina patients, and NSTEMI patients.
  • LMW-HA Stimulation: NSTEMI patients treated with LMW-HA showed a significant decrease in CD31 expression compared to their baseline (NT) levels. This indicates that LMW-HA triggers an inflammatory response in these patients.
  • HMW-HA Stimulation: Interestingly, HMW-HA did not produce the same effect. It did not cause a significant decrease in CD31 expression in any of the groups tested.
  • LPS Stimulation: As expected, E. Coli-LPS (a known inflammatory agent) significantly decreased CD31 expression in all groups, confirming its role as a positive control and validating the experimental setup.
These findings suggest that LMW-HA acts as a pro-inflammatory stimulus specifically in patients presenting with NSTEMI. This means that LMW-HA may contribute to the inflammatory cascade that damages the heart during an acute coronary event. While more research is needed, these results suggest that targeting the hyaluronan pathway could offer a novel therapeutic approach for managing inflammation in NSTEMI patients.

The Future of Hyaluronan Research in Heart Disease

The research into hyaluronan's role in heart disease is still in its early stages, but the initial findings are promising. Understanding how different sizes of HA affect inflammation in the heart could pave the way for new and more targeted therapies for conditions like NSTEMI. Future studies will likely focus on identifying specific enzymes involved in HA degradation and exploring the potential of HA-based therapies to either promote tissue repair or block excessive inflammation, depending on the specific context.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

Everything You Need To Know

1

What is hyaluronan (HA) and why is it relevant to heart health?

Hyaluronan (HA) is a naturally occurring substance found throughout the body, especially in the extracellular matrix. It's known for its roles in skin health and joint lubrication. Recent research reveals its complex role in cardiovascular health, specifically in acute coronary syndromes like Non-ST Elevation Myocardial Infarction (NSTEMI), making it a key focus in understanding and potentially treating heart inflammation. Its different molecular sizes, like High molecular weight HA (HMW-HA) and Low molecular weight HA (LMW-HA), have distinct biological activities, which further highlights its relevance.

2

How does hyaluronan contribute to inflammation in the context of NSTEMI?

In NSTEMI, Low molecular weight HA (LMW-HA) has been shown to act as a pro-inflammatory stimulus. Research indicates that when patients with NSTEMI are exposed to LMW-HA, they exhibit a significant decrease in CD31 expression on monocytes, which are involved in inflammation. This decrease in CD31 expression signals an inflammatory response. Unlike LMW-HA, High molecular weight HA (HMW-HA) did not produce the same effect, which suggests that the size of HA molecules influences their impact on the inflammatory processes within the heart during an acute coronary event.

3

What is the difference between High molecular weight HA (HMW-HA) and Low molecular weight HA (LMW-HA) concerning inflammation?

High molecular weight HA (HMW-HA) is generally considered to have anti-inflammatory properties, while Low molecular weight HA (LMW-HA) can paradoxically promote inflammation. The study mentioned indicates that LMW-HA specifically triggers an inflammatory response in NSTEMI patients, while HMW-HA did not elicit the same effect. This difference is critical as it shows how different HA sizes affect heart inflammation differently, offering potential targets for therapies.

4

What were the key findings of the study that investigated hyaluronan's impact in NSTEMI patients?

The study assessed the expression of CD31 on monocytes in three groups: healthy controls, stable angina patients, and NSTEMI patients. Under basal conditions, CD31 expression did not significantly differ between the groups. However, when stimulated with LMW-HA, NSTEMI patients showed a significant decrease in CD31 expression, indicating an inflammatory response. HMW-HA did not produce a similar effect. The experiment used E. Coli-LPS as a positive control, which confirmed the inflammatory response by significantly decreasing CD31 expression across all groups. This study's data highlights the specific pro-inflammatory role of LMW-HA in NSTEMI patients.

5

What are the potential future therapeutic implications of targeting the hyaluronan pathway in heart disease?

Targeting the hyaluronan pathway could offer novel therapeutic approaches for managing inflammation in conditions like NSTEMI. Understanding how different sizes of HA affect heart inflammation could lead to new and more targeted therapies. Future studies may focus on identifying enzymes involved in HA degradation and exploring HA-based therapies. This could include promoting tissue repair or blocking excessive inflammation, depending on the specific context. This approach has the potential to improve outcomes for patients with acute coronary syndromes by addressing the underlying inflammatory processes associated with the condition.

Newsletter Subscribe

Subscribe to get the latest articles and insights directly in your inbox.