Atherosclerosis - Pterostilbene & Progression of Artery Disease

Atherosclerosis is a chronic degenerative disease condition which slowly blocks arteries, accelerate aging and is a contributing factor in most age-related deaths.The key event in the  initiation and progression of atherosclerosis is injury and inflammation to the arterial lining (endothelial cells).

• Endothelial Cell Injury Reduction 
• Atherosclerosis is intrinsically linked to damage of the endothelial cells in the artery lining. Such damage is attributed to inflammation and oxidative stress in the arterial wall. In animal models, pterostilbene mitigated the process of atherosclerosis and reduced inflammation in the blood vessels. Importantly, pterostilbene increased levels of protective Nrf2 in the endothelial cells.(1)
• Vascular Inflammation Prevention 
•  In the gut, there are bacteria that convert choline and carnitine into  trimethylamine (TMA). In turn, TMA is converted to  trimethylamine-N-oxide (TMAO).(2) Increased levels of TMAO correlate to cardiovascular disease, by increasing vascular inflammation and endothelial dysfunction.(3)
• Pterostilbene significantly reduces vascular inflammation by:
• altering the composition of gut bacteria, thereby reducing the levels of TMAO
•  decreasing inflammatory vascular markers, including TNF-alpha.(4)
• Protects Against Oxidized Low Density Lipoprotein (LDL) 
• Oxidized LDL targets the endothelium lining of the artery and causes cellular death of the endothelium. This facilitates atherosclerosis development. Pterostilbene inihibits expression of LOX-1, the cellular receptor for oxidized LDL in the endothelium. As such, pterostilbene mitigates the buildup of LDL and subsequent atherosclerosis.(5). 
• Attenuates Heart Aging (Myocardial Fibrosis)
• Oxidative stress negatively impacts heart function and accelerates aging of the heart. As a result of oxidative stress, including inflammation, the heart can become fibrotic, replacing heart tissue with non functional fibrotic tissue.  In lab studies pterostilbene has been shown to mitigate myocardial fibrosis.(6)

CURCUMIN PXC  (Pterostilbene)

REFERENCES

(1) Tang T, et al. Pterostilbene reduces endothelial cell injury in vascular arterial walls by regulating the Nrf2-mediated AMPK/STAT3 pathway in an atherosclerosis rat model. Exp Ther Med. 2020 Jan

(2) Rath S, et al. Potential TMA-Producing Bacteria Are Ubiquitously Found in Mammalia. Front Microbiol. 2020 Jan 

(3) Singh G, et al.  High Mobility Group Box 1 Mediates TMAO-Induced Endothelial Dysfunction. Int J Mol Sci 2019 Jul

(4) Koh YC, et al.  Prevention of Vascular Inflammation by Pterostilbene via Trimethylamine-N-Oxide Reduction and Mechanism of Microbiota Regulation.  Mol Nutr Food Res. 2019 Oct.

(5) Zhang L, et al.  Pterostilbene protects vascular endothelial cells against oxidized low-density lipoprotein-induced apoptosis in vitro and in vivo. Apoptosis. 2012 Jan

(6) Kang LL, et al. Pterostilbene Attenuates Fructose-Induced Myocardial Fibrosis by Inhibiting ROS-Driven Pitx2c/miR-15b Pathway. Oxid Med Cell Longev. 2019 Dec

Remarkable Vinpocetine & Citrus Bergamot - Youthful Arteries and Suppressing Atherosclerosis

Arteries degenerate with age, via a process known as vascular remodeling, leading to atherosclerosis, stroke and other cardiovascular diseases.. Therefore, preserving youthful arteries is a very important factor in longevity. Two important supplements which have been shown to suppress degenerative changes to the arteries are vinpocetine and citrus bergamot polyphenols.

VASCULAR AGING - Involves changes to the vascular endothelium and smooth muscle which promotes increased hypertension and stiffness of the arteries. The results is an aged vascular system  which is characterized by inflammation and atherosclerosis. As such, the arteries lose their ability to expand and contract, and becomes stiff, thickened and inflamed. When the vascular system ages it becomes more susceptible to hypertension, ischemic stroke and coronary heart blockage (heart attack). Furthermore, vascular aging in the brain may lead to cognitive disorders due to diminished blood flow.

Key areas of Vascular Aging:

• NF-kB - The master transcription factor for promoting inflammation in the artery and is involved in atherosclerosis plaque progression.
• PDE1 (phosphodiesterase) - An isozyme which plays a key role in the pathological changes which occur in the vascular structure with age. Increased levels of PDE1 are associated with loss of vasodilator function, vascular smooth muscle senescence, increased blood pressure and vascular hypertrophy. (1,2)

VINPOCETINE -
Promotes youthful arteries via two mechanisms. Vinpocetine reduces the release of inflammatory cytokines from endothelial cells and vascular smooth muscle by targeting oxidative stress and inflammation of the arteries. NF-kB. Also, vinpocetine is a powerful inhibitor of PDE1.

• Suppresses Atherosclerosis - Via the inhibition of inflammation transcription factor NF-kB.(3)
• Inhibition of PDE1 - PDE1 is a key regulator in the pathological changes that occur in aging vascular functioning including changes to structure and blockage of blood flow. Aging (senescent) vascular cells are correlated with increased levels of PDE1. (4) Inhibition of PDE1 has been shown to reduce all biomarkers associated with vascular aging.

CITRUS BERGAMOT (Bergamonte®) - The polyphenols in Citrus Bergamot uniquely provide artery anti-aging benefits. Citrus Bergamot provides protection directly to the vascular endothelium, in addition to optimizing cholesterol and triglycerides and inhibiting non alcoholic liver disease.

• Vascular Endothelium Protection.  Targets arterial endothelium cells to reduce inflammation and oxidative stress. Both are associated with vascular aging.
• Inhibits Non Alcoholic Fatty Liver Disease (NAFLD). NAFLD is a common liver disease where fat accumulates in the liver, causing liver dysfunction and is correlated with increased cardiovascular disease and mortality. It is estimated that up to 25% of Americans have NAFLD. Furthermore, excess belly fat not only is predictor of increased cardiovascular risk, but normally indicates high fat in the liver and NAFLD.
• Bergamot polyphenols stimulate lipid metabolism thereby preventing toxic build-up in the liver. Removal of lipids is through enhanced autophagy. (6)
  
• Decreases Oxidized Cholesterol Receptors. LOX-1 is the receptor on the endothelium for oxidized cholesterol. Expression of LOX-1 is increased with pathological conditions including hypertenison, hyperlipidemia, and diabetes.(5, 7)
• Inhibits Phosphodiesterases (PDEs). Offers similar protections as vinpocetine in preventing age-related changes to vascular structure .(7)

 VASCULAR STRENGTH  (with Vinpocetine and Bergamot Polyphenols)

REFERENCES:

(1) Chan S, et al. PDE1 isozymes, key regulators of pathological vascular remodeling. Curr Opin Pharmacol. 2011 Dec

(2) Bautista N, et al. Phosphodiesterase 1 regulation is a key mechanism in vascular aging. Clin Sci (Lond) 2015 Dec

(3) Zhuang J, et al. Inhibitory effects of vinpocetine on the progression of atherosclerosis are mediated by Akt/NF-κB dependent mechanisms in apoE-/- mice. PLoS One. 2013 Dec.

(4) Yan, C. Cyclic nucleotide phosphodiesterase 1 and vascular aging. Clin Sci (Lond). 2015 Dec.

(5) Chen M, et al. LOX-1, the receptor for oxidized low-density lipoprotein identified from endothelial cells: implications in endothelial dysfunction and atherosclerosis. Pharmacol Ther. 2002 Jul

(6) HP Ingredients. Support against NAFLD in those with Metabolic Syndrome. 2016 Apr.

(7) HP Ingredients. 2016.