Information Classification: General

DERRICK
DESILVA, MD
Associate Attending Staff
Raritan Bay Medical
Ctr., Perth Amboy, NJ
Teaching Faculty JFK
Medical Center,
Edison, NJ

The Endothelial
Glycocalyx
A new discovery with vast implications for
metabolic health
IMPORTANT NOTICE:
This information is for licensed healthcare practitioner education only and is not to be disseminated to the general public.
Views expressed are the speaker’s own.
Disclosure

• Worked with and was compensated by Calroy Health Sciences on the development of
vascular education materials
Learning Objectives

1. Assess research on the endothelial glycocalyx and vascular health

2. Integrate the glycocalyx connection with metabolic health and dysfunction
3. Describe the value of extending the duration of effect for nitric oxide support
Prevalent

70.0% of major CVD events in the United States were

attributable to low and moderate cardiovascular
health

Nearly half of US adults have elevated blood pressure

(47%)

Tsao et al. Heart Disease and Stroke Statistics—2022 Update: A Report From the American Heart Association. Circulation.
2022;145(8):e153-e639. doi:10.1161/CIR.0000000000001052
Centers for Disease Control and Prevention. Hypertension Cascade. Atlanta, GA: U.S. Department of Health and Human Services; 2021.
What is the role of the endothelial layer?

• The vascular endothelium covers ALL the luminal surface

of blood vessels and lymphatics
• It is considered the largest metabolically active organ of
the body
What is the role of the endothelial layer?

• The vascular endothelium covers ALL the luminal surface

of blood vessels and lymphatics
• It is considered the largest metabolically active organ of
the body
• The endothelium produces vasoactive substances to
maintain vascular tone and regulate blood flow to the
tissues and organs.
• Oxidative stress damages the endothelium and leads
to endothelial dysfunction
• This endothelial dysfunction is the hallmark of all
cardiovascular diseases.
What is the role of the endothelial layer?

• The vascular endothelium covers ALL the luminal surface

of blood vessels and lymphatics
• It is considered the largest metabolically active organ of
the body
• The endothelium produces vasoactive substances to
maintain vascular tone and regulate blood flow to the
tissues and organs.
• Oxidative stress damages the endothelium and leads
to endothelial dysfunction
• This endothelial dysfunction is the hallmark of all
cardiovascular diseases.
• All cardiovascular risk factors are associated with
endothelial dysfunction that precedes the development of
morphological vascular changes and manifestation of
cardiovascular diseases.
THE DAWN OF MICROVASCULAR IMAGING
IMPROVED RESOLUTION
REVEALS AN INVISIBLE
BARRIER
The Endothelial Glycocalyx (EGX): Sentinel and Protector

Where Endothelial
A microscopically thin gel-like layer of glycoproteins, proteoglycans, and
Dysfunction Starts
GAGs coating the luminal side of the vascular endothelium

EGX damage precedes endothelial damage

Endothelial Glycocalyx:

• Regulates permeability as a selective

sieving barrier

• Helps regulate surface inflammatory

response

• Arterial anti-adhesive

• Harbors coagulation regulatory factors

• Houses extracellular SOD – potent

anti-inflammatory antioxidant enzyme

• Triggers production of nitric oxide

(NO) through classical, enzymatic

eNOS pathways
Compromised Glycocalyx:
• Reduced NO availability

• Increased oxidative stress

• Increased leakage of macromolecules

• Increased platelet adherence

• Increased thrombin generation

• Increased leukocyte adhesion &

diapedesis
The EGX & Nitric Oxide
Classic eNOS Production

• Endothelial cells produce nitric oxide in

response to blood flow within the lumen

• This is dependent upon the body’s sensor

for detecting shear stress: the endothelial
glycocalyx (EGX)

• A healthy EGX is required to trigger

eNOS and produce nitric oxide

• A healthy EGX harbors the antioxidant

superoxide dismutase (ecSOD)

D. DeSilva, et al. Anti-Aging Medical News (2016) Winter:92-95

• NO production declines with age

Cause and Consequence of Endothelial Dysfunction

Dysfunctional
Risk factors/ endothelial
oxidative glycocalyx
stress

Decreased
Endothelial
NO
dysfunction
production

Widespread
vascular
damage
Going Upstream: Supporting The Endothelial Glycocalyx

The endothelial glycocalyx is both fragile and resilient

Like the microbiome, with the right support it can be
healed, but it is subject to constant insults

Improving lifestyle, reducing inflammation, controlling blood

pressure and glucose regulation are all beneficial
 Identifying
Glycocalyx-Regenerating Compounds (GRCs)

GRCs from polysaccharides

Marine-based
with similar structure to the
polysaccharides have been
glycosaminoglycans found in the
shown to be excellent GRC
human endothelial glycocalyx
candidates and have
are logical candidates
additional cardiovascular
benefits

Banerjee et al. Ind Eng Chem Res. 2021;60(48):17328-17347. doi:10.1021/acs.iecr.1c03074

Cancel &Tarbell. The FASEB Journal. 2013;27(S1):896.3-896.3. doi:https://doi.org/10.1096/fasebj.27.1_supplement.896.3
Florez et al.. Curr Med Chem. 2017;24(2):149-175. doi:10.2174/0929867323666161028160416
Okamoto et al. J Nat Med. 2019;73(3):614-619. doi:10.1007/s11418-019-01289-5
Patil et al.. Front Cardiovasc Med. 2018;5. doi:10.3389/fcvm.2018.00153
Tool to screen and study Glycocalyx-Regenerating
Compounds (GRCs)

• Micro-fluidic chip high-throughput

testing platform
• Allows for rapid screening
of multiple compounds in
parallel channels that mimic
blood vessel sizes
• Can experimentally control
blood flow to evaluate
different shear stresses
• Made of living human endothelial
cells with endothelial glycocalyx
• Evaluated many compounds to
find the one with the best
protective and restorative effect
Rhamnan sulfate from Monostroma nitidum: Powerful and safe

A wide variety of marine-based polysaccharides were

tested for their effect on the EGX
Including: Fucoidan from brown seaweed and
Rhamnan sulfate from green seaweed

Rhamnan sulfate from Monostroma nitidum consistently

exhibited the desired combination of powerful and safe
EGX protective and regenerative properties
Rhamnan sulfate from Monostroma nitidum is extremely
well-tolerated in humans, with no known safety concerns
 Key Takeaways
• EGX damage precedes endothelial dysfunction
• EGX is intricately related to NO production
• Rhamnan sulfate from Monostroma nitidum is a powerful
and safe glycocalyx-support compound

Healthy Artery EGX support provides:

• Foundational for vascular health
• Endogenous production of NO
• Bioavailability of NO by harboring ecSOD
Vascular Health Upstream Intervention #2: Nitric Oxide Support

Nitric Oxide
An essential signaling molecule - interacts with
and modifies many processes
System-wide effects
Critical for vasodilation
When NO production declines, endothelial
dysfunction follows, threatening multiple organs
and systems
 Nitric Oxide
“Are we as old as our NO?”

Nitric oxide production declines with:

“Impaired
• Aging
generation and
• Inflammation and chronic illness signaling of nitric
oxide contribute
• Standard American diet and/or sedentary lifestyle substantially to
cardiovascular
• Chronic smoking risk.”

• Many other factors…

-Sverdlov et al.

Sverdlov et al. Aging of the Nitric Oxide System: Are We as Old as Our NO? J Am Heart Assoc. 2014;3(4):e000973.
doi:10.1161/JAHA.114.000973
Toda et al. Nitric oxide-mediated blood flow regulation as affected by smoking and nicotine. Eur J Pharmacol. 2010;649(1-3):1-13.
doi:10.1016/j.ejphar.2010.09.042
Nitric Oxide
The Key Endothelium-Derived Relaxing Factor
Sufficient Nitric Oxide:
● Vasodilating
● Anti-thrombogenic
● Anti-inflammatory
● Anti-adhesive (inhibits Nitric oxide deficiency
Deficient Nitric Oxide: leukocyte-endothelial
● Vasoconstricting adhesion and platelet – due to decreased
● Pro-thrombotic aggregation) NO synthesis and
● Pro-inflammatory ● Antioxidative bio-availability –
● Pro-adhesive ● Anti-mitogenic
● Pro-oxidative
● Proliferative
is at the center of
endothelial
dysfunction and the
loss of endothelial
homeostasis
Nitric Oxide: Barometer and Lever

• Nitric oxide offers an early opportunity to evaluate and work with patients to improve
vascular wellness

• Salivary tests offer rapid feedback

• NO production is also relatively easy to affect with both lifestyle and supplementation,

offering a lever for rapid improvements

 Salivary Response of Typical Nitrite (NO2)- and Nitrate (NO3)-
Based Products

Onset of Action
Time to reach effective
concentration
(above 220 μM)
Peak Concentration
The highest concentration
reached
Time to Peak
Time to reach the highest
concentration
Area under the Curve
Total Bioavailability

Estimated curves are based on the experimental data generated from typical products on the market.
 Salivary Response of Typical Nitrite (NO2)- and Nitrate (NO3)-
Based Products

Onset of Action
Time to reach effective
concentration
(above 220 μM)
Peak Concentration
The highest concentration
reached
What’s needed for compliance and optimized NO?
Time to Peak
Time to reach the highest
concentration
Area under the Curve
Total Bioavailability

Estimated curves are based on the experimental data generated from typical products on the market.
Target: 24-hour optimized nitric oxide

Supporting the body’s natural pathways

● NO is an incredibly short-lived gaseous signalling

molecule

● Yet the vascular system needs ongoing, optimized

support for blood flow and oxygenation
Takeaways
• A healthy endothelial glycocalyx is vital to human
health and longevity
• A healthy glycocalyx is key to ongoing nitric oxide
release
• Even with a healthy glycocalyx, many need additional
NO support

All of this is increasingly important as we age, and in

individuals with chronic inflammation