6 weeks consumption of pure fresh coconut milk caused up-regulation of eNOS and CSE protein expression in middle-aged male rats

I only copied the abstract and discussion portion, much more at link. What the hell is your doctor and stroke hospital going to do to get this tested in humans? Or will they DO NOTHING like usual? It is not their problem to solve? YOU are on your own to solve it, get going. 

6 weeks consumption of pure fresh coconut milk caused up-regulation of eNOS and CSE protein expression in middle-aged male rats

Chaweewan Jansakul^{1  2} 

Jomkarn Naphatthalung^{1  2} 

Sakda Pradab^{1  2} 

Somruedee Yorsin⁵ 

Kanyanatt Kanokwiroon^{3  4} 

¹ Faculty of Traditional Thai Medicine, Prince of Songkla University, Hat-Yai, Thailand

² Natural Product Research Centre of Excellence, Prince of Songkla University, Hat-Yai, Thailand

³Department of Biomedical Sciences, Faculty of Medicine, Prince of Songkla University, Hat-Yai, Thailand

⁴The Excellent Research Laboratory of Cancer Molecular Biology, Prince of Songkla University, Hat-Yai, Thailand

⁵Faculty of Medicine, Princess of Naradhiwas University, Narathiwas, Thailand

ABSTRACT

Coconut milk (CCM) has been an important cooking ingredient in the Asia-Pacific region since ancient time. Due to its high content of saturated fatty acids, it has been considered atherogenic. We have tested if chronic consumption of fresh coconut milk by middle-aged male rat affects vascular function, plasma glucose and lipid profiles. Compared to control, CCM caused lower maximal contraction to phenylephrine of thoracic aortic rings and increased relaxation to acetylcholine that was abolished by N ^G-nitro-L-arginine (L-NA) or disruption of the endothelium. DL-propargylglycine caused slight increase in baseline tension of L-NA treated aortic rings of CCM-treated rats and produced higher contractile response of the aortic rings to low concentrations of phenylephrine. The aortic eNOS- and cystathionine-γ-lyase(CSE) proteins expression of the CCM-treated rats were also higher than in controls. Except for lower fasting plasma glucose there were no changes in blood chemistry for the CCM treated rats. CCM consumption caused up-regulation of eNOS and CSE protein expression which resulted in increased production of NO and H₂S from the blood vessels with attenuation of vasocontraction to phenylephrine and increased relaxation to acetylcholine. These novel benefits may be expected to reduce the development of cardiovascular risk factors in the aging rat.

Discussion

The present study demonstrated that consumption of the CCM caused beneficial effects on the cardiovascular system if consumed in a sufficient amount. As shown in the results section, consumption of the CCM at a dosage of 1 g/kg for 6 weeks by the middle-aged rats did not result in any difference in the parameters studied. When the dosage was increased to 3 g/kg, CCM caused lowered food intake.The reduction in food intake was not associated with any change in body weight or in the weight of the organs measured. The reasons for this might be due to high lipid content (70%) of the CCM composition which consists dominantly of medium chain fatty acids (8: 0 to 12: 0; 45%). These fatty acids are absorbed directly to the portal vein except for lauric acid (C12:0) that is partly absorbed via the lymphatic system (^{Mu, Hoy, 2000}; 2001; 2002). More recently, ^{Valente et al. (2017}) reported that coconut oil consumption promoted less appetite in women with excess body fat. In addition, Jambor de Sousa et al. (2006) found that hepatic portal vein infusion of caprylic acid, a medium chain fatty acid, caused reduction of food intake by about 40% in 18-h food-deprived male rats. Another possibility is that CCM might contain an active substance that at high doses it causes satiety or reduced appetite resulting in reduced food intake. However, further specific studies would be needed to clarify these possibilities.
The alteration in vascular function, especially endothelial function, is the key event in the pathophysiology of atherosclerosis, as it was shown that endothelial dysfunction preceded and predicted atherosclerosis (^{Bonetti, Lerman, Lerman, 2003}; ^{Davignon,Ganz, 2004}).In the present study endothelial dysfunction of the middle-aged male rat(^{Chongsa et al., 2015}) was used to study the effects of chronic consumption of the CCM.Although there were no changes in animal blood pressure and heart rate after taking CCM compared to the distilled water control group, adosage of 3 g/kg but not 1g/kg of CCM, caused some beneficial changes in vascular function. These included reduction in maximal contractile response of thoracic aortic rings to phenylephrine and a higher maximal relaxation to acetylcholine. These effects were abolished by L-NA or removal of the endothelium, which indicates that the lowering of maximal contractile response to phenylephrine of the CCM-treated aortic rings might be due to an increase in nitric oxide production from the vascular endothelium. This was confirmed by the finding that eNOS protein expression of the thoracic aorta obtained from CCM-treated was higher than that of the control rats.^{Salil, Nevin, Rajamohan (2011}, 2012)reported that coconut kernel protein is rich in arginine which was able to rescue the pancreatic β-cells and cytoarchitecture in alloxan-induced diabetic Wistar Albino rat via the arginine-nitric oxide pathway. Thus, it is possible that the up-regulation of the vascular eNOS of the CCM treated middle-aged rat in the present study might be mediated by the coconut protein. However, further study of the isolated CCM protein consumption by the middle-aged rat would be needed to clarify this possibility.
It has been reported that high-fat diet consumption by young rats or mice for 12-14 weeks causes deficiency of aortic CSE and H₂S (^{Jenkins, Nguyen, Hart, 2016}; ^{Peh et al., 2014}). Thus, it is possible that chronic consumption by the middle-aged rat of the CCM which contained high content of coconut oil might affect blood vessel H₂S production. To test this possibility another set of the endothelium-intactaortic rings was used and preincubated with L-NA in order to inhibit eNOS activity in order to prevent any disturbances by nitric oxide before adding PAG, a cystathionine-γ-lyase inhibitor; the vasocontraction to phenylephrine was then determined. As shown in the results section, adding PAG to the incubation medium caused a greater increase in basal baseline tension of the aortic rings obtained from CCM-treated rats than that of the control group, suggesting that the activity of the CSE enzyme of the CCM-treated rats was higher than that of the control rats. These results sequentially caused an increase in contractile response to low concentrations of the phenylephrine on the aortic rings that was higher than that of the control group. The finding that the blood vessel CSE protein expression was higher in the CCM treated rats is consistent with the finding that consumption of CCM caused an increase in blood vessel H₂S production. This result is in contrast to those of the Jenkins, Nguyen, Hart(2016) and Peh et al.(2014) who found that high fat diet caused a decrease in vascular CSE and H₂S production.The reason for this might be the differences in the types of fatty acid used. In the present study we used CCM which contained mostly medium-chain fatty acid which was found to cause an increase in mitochondrial and peroxisomal β-oxidation of fatty acids (^{Arunima, Rajamohan, 2014}). In contrast, Jenkins, Nguyen, Hart (2016) and Peh et al.(2014) used western diet and high fat diet, respectively, which contained mostly long-chain fatty acid, which was found to induce vascular oxidative stress and reduce endothelial function. As another possibility, ^{Zhao et al. (2001}) found that endogenous H₂S production from different vascular tissues including thoracic aorta was enhanced by the NO. Thus, the increased CSE protein expression which resulted in an increased H₂S production in the present study might be facilitated by the increased NO production elicited by the CCM, as mentioned above. However, further study is needed to clarify these possibilities.
In the present study it was also found that chronic consumption of CCM caused a slight decrease in basal fasting plasma glucose compared to that of the control group. As mentioned above, the reason for this might be due to the increase in basal level of NO since it has been reported that low concentration of NO exerted positive regulation of insulin sensitivity and secretion (^{Carvalho et al., 2016}; ^{Kurohane Kaneko, Ishikawa, 2013}). However, to clarify this possibility, further studyto measure basal plasma insulin level and/or the glucose insulin sensitivity of the CCM-treated and the control middle-aged rats would be necessary.
Taken together, consumption of CCM at the dosage of 3 g/kg increased blood vessel eNOS and CSE protein expression resulting in increased NO and H₂S production to attenuate the contractile response of thoracic aortic rings to phenylephrine and potentiate vasodilatation to acetylcholine, all of which could be expected to prolong vascular health of the middle-aged rat. In addition, CCM consumption caused lowering of plasma glucose level with no harm to liver or kidney functions, or on fat metabolism. Thus, CCM could be a novel food to develop as a nutraceutical for vascular health of the aging human being. Nevertheless, further work is required to identify the mechanism that causes CCM to lower plasma glucose and the vascular effects described.

 

Systems Biology and Noninvasive Imaging of Atherosclerosis

I couldn't tell at all from this limited part of the article what to ask my doctor to do to image my arteries to see what risks I have. 

Systems Biology and Noninvasive Imaging of Atherosclerosis

1. Claudia Calcagno,
2. Willem J.M. Mulder,
3. Matthias Nahrendorf,
4. Zahi A. Fayad

+ Author Affiliations

1. From the Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY (C.C., W.J.M.M., Z.A.F.); Department of Medical Biochemistry, Academic Medical Center, Amsterdam, The Netherlands (W.J.M.M.); and Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA (M.N.).

1. Correspondence to Claudia Calcagno, MD, PhD, Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029. E-mail claudia.calcagno@mssm.edu

Key Words:

• atherosclerosis
• cardiovascular diseases
• inflammation
• lipids
• risk factors

Atherosclerosis is a systemic disease of the arterial vessel wall. Although the mortality due to cardiovascular events is decreasing, the prevalence of atherosclerosis and its comorbidities, and the consequent heath care costs are expected to rise sharply in the near future.¹

Because the precise cause and pathogenesis of this complex, multifactorial disease are still not fully understood, the clinical assessment of cardiovascular risk has been traditionally based on population risk factors (RFs).² However, this approach still largely fails to capture the individual’s cardiovascular risk: most cardiovascular events occur in patients with 1 or few traditional RFs, whereas individuals classified as high risk may never experience clinical events.³

The past 10 years have seen a significant paradigm shift in our understanding of the mechanisms of atherogenesis. From being considered the mere result of passive lipid accumulation in the vessel wall, atherosclerosis is now classified as an active inflammatory condition.^4,5 The presence of abundant, active inflammatory cells is a known hallmark of high risk, vulnerable atherosclerotic plaques.^4,5 Many studies have identified several systemic proinflammatory conditions (such as lupus,⁶ rheumatoid arthritis,^7–9 and primary cardiovascular events themselves¹⁰) as emerging, independent RFs for atherosclerosis. New evidence suggests that atherosclerosis arises from the complex influence of genetic, environmental, and behavioral variables on systemic and local inflammation through a complex network of molecules, cells, and organs. 

Thanks to the recent technological advancements of high-throughput ‘-omics’, a plethora of the genes, proteins, and cells …

[Full Text of this Article]

Primary Prevention of Atherosclerosis - A Clinical Challenge for the Reversal of Epigenetic Mechanisms

And maybe we will finally get to the beginning cause of this and fix that rather than this stupidity of statin lowering.


http://circ.ahajournals.org/content/125/19/2363.full

1. Claudio Napoli, MD, PhD, MBEth;
2. Valeria Crudele, BiolD;
3. Andrea Soricelli, MD;
4. Mohammed Al-Omran, MD;
5. Nicoletta Vitale, PhD;
6. Teresa Infante, BiolD;
7. Francesco P. Mancini, MD, PhD

+ Author Affiliations

1. From the Department of General Pathology, Excellence Research Centre on Cardiovascular Diseases, U.O.C. Immunohematology, Transfusion Medicine and Transplant Immunology, Regional Reference Laboratory of Transplant Immunology, Azienda Universitaria Policlinico, 1st School of Medicine, Second University of Naples, Naples, Italy (C.N., V.C.); Fondazione SDN, Istituto di Ricovero e Cura a Carattere Scientifico, Naples, Italy (C.N., A.S., T.I.); Parthenope University, Naples, Italy (A.S.); Peripheral Vascular Disease Research Chair, College of Medicine, King Saud University, Riyadh, Saudi Arabia (M.A.-O.); and Department of Sciences for Biology, Geology, and Environment, University of Sannio, Benevento, Italy (N.V., F.P.M.).

1. Correspondence to Professor Claudio Napoli, MD, PhD, Department of General Pathology, Excellence Research Centre on Cardiovascular Diseases, 1st School of Medicine, Complesso S. Andrea delle Dame, Second University of Naples, Piazza Miraglia 2, 80138 Naples, Italy. E-mail claudio.napoli@unina2.it or claunap@tin.it

Key Words:

• primary prevention
• epigenetics
• statins

Innovative advances in understanding the pathogenesis of atherosclerosis have been achieved over the past 25 years. Although elevated levels of serum low-density lipoprotein cholesterol (LDL-C) are the major cause of onset of the disease, as established by a large number of superb epidemiological, clinical, and experimental studies, important novel factors have entered the arena of the atherogenic process. Besides the historical oxidative hypothesis that states that oxidized LDL, by escaping the homeostatic mechanism, strongly accelerates plaque formation, more recent evidence has given credit to vascular inflammation and apoptosis as crucial players in the progression of atherosclerosis.^1–3 The disease has also been linked to the subintimal infiltration of immune cells and endothelial dysfunction induced by cardiovascular risk factors. Currently, endothelial dysfunction is considered one of the first stages of vascular damage and an early event in atherogenesis.^1–3 Etiologic and pathogenetic factors, of both genetic and environmental origin, act together to promote local and systemic effects that lead to the onset, progression, and final outcome of the atherosclerotic disease. The clinical sequelae of atherosclerosis, myocardial infarction, stroke, and peripheral arterial disease depend on the affected vascular district, which in turn depends on complex gene-environment interplay.
Despite the sudden occurrence of clinical symptoms, however, the evolution of atherosclerosis is very slow, which provides an opportunity for early diagnosis. In fact, a breakthrough in the field has been to recognize that although atherosclerosis generates severe diseases that most frequently affect middle-aged to old people, atherogenesis begins very early in life, even at the fetal stage.^4,5 Primary prevention of any disease is more effective if started sooner. Therefore, it is of paramount importance to identify high-risk individuals and to initiate primary prevention in a timely manner, especially for atherosclerosis, which can begin its slow but relentless damage of the arterial wall even before birth. Epigenetic mechanisms have been recognized recently as possible modifiers of the risk of developing premature atherosclerosis. Therefore, the recognition of epigenetic markers that reveal a tendency to vascular diseases could be an effective aid in the early detection of at-risk individuals. These people can then be targeted for both lifestyle changes and pharmacological treatments to prevent or delay atherosclerotic disease. Although the pharmaceutical industry has provided invaluable preventive and therapeutic tools, general rules of best practice dictate that life habits be modified first, and only if intermediate markers of the disease do not normalize should at-risk individuals be given drug therapy. This approach also allows reducing the health care expenditure on the primary prevention of atherosclerosis-related disease.

Previous SectionNext Section

Early Onset of Human Atherogenesis

The prodromal stages of human atherosclerotic lesions are already set during fetal development.^6–8 A seminal observation was that maternal hypercholesterolemia is associated with increased formation of fatty streaks in fetal arteries, which suggests that hypercholesterolemia is atherogenic even before birth.⁹
Fetal lesions occur in the same arterial districts as those of adolescents and adults and are histologically similar to lesions that occur later in life.¹⁰ Moreover, there is evidence that fetal lesions can partially regress during the final stages of pregnancy or early infancy, when cholesterol levels are low.⁸ Atherosclerosis is significantly accelerated in children of mothers with high serum cholesterol compared with children of mothers with normal serum cholesterol. The mechanism by which maternal hypercholesterolemia can promote development of lesions in offspring has been explored in animal models.^11–13 Indeed, lesions doubled in a litter of hypercholesterolemic mother rabbits compared with normocholesterolemic mother rabbits, and there was a linear correlation between maternal cholesterol and vascular injuries at birth.¹¹ Consistently, a similar correlation was observed in LDL receptor–deficient mice.¹³ Maternal cholesterol levels increase physiologically from the first trimester and throughout the pregnancy, even in mothers with normal serum cholesterol levels¹⁴; this increase is much greater in mothers who are already hypercholesterolemic before pregnancy. Microarray analysis of aortas has shown that many genes are elevated or inhibited in the offspring of hypercholesterolemic mothers.¹⁵
Children and young adults are also vulnerable to the effects of cardiovascular risk factors and show early signs of atherosclerosis, which becomes a complex process driven by conventional risk factors.¹⁶ Among cardiovascular risk factors, body mass index, systolic and diastolic blood pressure, serum total cholesterol, triglycerides, LDL-C, and high-density lipoprotein cholesterol are strongly associated with the extension of lesions in the aorta and coronary arteries. In addition, the severity of aortic and coronary artery disease in young people increases in proportion to the number of cardiovascular risk factors they face.⁶

Much more at link.

Effects of a Pomegranate Fruit Extract rich in punicalagin on oxidation-sensitive genes and eNOS activity at sites of perturbed shear stress and atherogenesis

So maybe pomegranate and watermelon juice could naturally reduce your plaque. What does your doctor think?
http://cardiovascres.oxfordjournals.org/content/73/2/414.short
The following line from the full text;
Regular pomegranate juice administered to hypertensive patients caused
a significant drop in blood pressure [26], a reduction in carotid plaque development [27] 
The abstract here:

1. Filomena de Nigris^a,^b,
2. Sharon Williams-Ignarro^c,
3. Vincenzo Sica^a,^b,
4. Lilach O. Lerman^d,
5. Francesco P. D'Armiento^e,
6. Russell E. Byrns^f,
7. Amelia Casamassimi^a,^b,
8. Daniela Carpentiero^a,
9. Concetta Schiano^a,
10. Daigo Sumi^f,
11. Carmela Fiorito^a,
12. Louis J. Ignarro^f and
13. Claudio Napoli^a,^b,*

+ Author Affiliations

1. ^aDepartment of General Pathology, School of Medicine, University of Naples, 80134 Italy
2. ^bExcellence Research Center of Cardiovascular Diseases, II University of Naples, Italy
3. ^cDivision of Anesthesiology University of California, Los Angeles, CA 90095, United States
4. ^dDivision of Hypertension, Mayo Clinic Foundation, Rochester, MN 55095, United States
5. ^eDepartment of Human Pathology, School of Medicine, University of Naples, 80134 Italy
6. ^fDivision of Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90095, United States

1. *Corresponding author. Department of General Pathology, School of Medicine, University of Naples, 80134 Italy. Email address: claunap@tin.it

• Received April 14, 2006.
• Revision received August 19, 2006.
• Accepted August 25, 2006.

Abstract

Background: Atherosclerosis is enhanced in arterial segments exposed to disturbed flow. Perturbed shear stress increases the expression of oxidation-sensitive responsive genes (such as ELK-1 and p-CREB). Polyphenolic antioxidants contained in the juice derived from the pomegranate contribute to the reduction of oxidative stress and atherogenesis during disturbed shear stress.

Aim of the study: To evaluate the effects of intervention with the Pomegranate Fruit Extract (PFE) rich in polyphones (punicalagin, which is a potent antioxidant) on ELK-1, p-CREB, and endothelial nitric oxide synthase (eNOS) expression induced by high shear stress in vitro and in vivo.

Results: At the doses used in the study, both the PFE and the regular pomegranate juice concentrate reduced the activation of ELK-1 and p-CREB and increased eNOS expression (which was decreased by perturbed shear stress) in cultured human endothelial cells and in atherosclerosis-prone areas of hypercholesterolemic mice. PFE and pomegranate juice increased cyclic GMP levels while there was no significant effect of both compounds on the conversion of l-arginine to l-citrulline. Administration of these compounds to hypercholesterolemic mice significantly reduced the progression of atherosclerosis and isoprostane levels and increased nitrates. This protective effect was relevant with PFE. Vasomotor reactivity was improved and EC₂₅ values in response to Ach and NONOate were significantly increased in treated mice in comparison to controls.

Conclusion: This study indicates that the proatherogenic effects induced by perturbed shear stress can be also reversed by chronic administration of PFE.