Hypoascorbemia induces atherosclerosis and vascular deposition of lipoprotein(a) in transgenic mice

John Cha, Aleksandra Niedzwiecki, Matthias Rath
Dr. Rath Research Institute, 1260 Memorex Drive, Santa Clara, CA 95050
American Journal of Cardiovascular Medicine 2015;5(1):53-62

www.AJCD.us /ISSN:2160-200X/AJCD0007056

Abstract: Lipoprotein(a), a variant of LDL carrying the adhesive glycoprotein apo(a), is a leading risk factor for cardiovascular disease. Lipoprotein(a) (Lp(a)) is found in humans and subhuman primates but rarely in lower mammals.

Read more: Hypoascorbemia induces atherosclerosis and vascular deposition of lipoprotein(a) in transgenic mice

Inhibition Of Collagen Synthesis By Select Calcium And Sodium Channel Blockers Can Be Mitigated By Ascorbic Acid And Ascorbyl Palmitate

V. Ivanov, S. Ivanova, T. Kalinovsky, A. Niedzwiecki and M. Rath
Dr. Rath Research Institute, 1260 Memorex Drive, Santa Clara, CA 95050
American Journal of Cardiovascular Medicine 6(2):26-35, 2016

Abstract: Calcium, sodium and potassium channel blockers are widely prescribed medications for a variety of health problems, most frequently for cardiac arrhythmias, hypertension, angina pectoris and other disorders. However, chronic application of channel blockers is associated with numerous side effects, including worsening cardiac pathology. For example, nifedipine, a calcium-channel blocker was found to be associated with increased mortality and increased risk for myocardial infarction.…

Read more: Inhibition Of Collagen Synthesis By Select Calcium And Sodium Channel Blockers Can Be Mitigated By Ascorbic Acid And Ascorbyl Palmitate

Nutrient supplementation modulates angiotensin II-mediated atherosclerosis in ApoE KO mice

V. Ivanov, J. Cha, S. Ivanova, T. Kalinovsky, M. Rath, A. Niedzwiecki
Molecular Medicine Reports 3:417-425, 2010

Abstract:
We studied the effect of nutrient / herbal extract mixture (NM) supplementation prior to angiotensin II (AngII) administration on ApoE KO mice. AngII-mediated injuries, which included increased atherosclerotic lesion size (by 31%) and severity (by 200%) as well as increased number of necrotic cores (by 44%), were attenuated by NM supplementation, resulting in reduced lesion size by 20% (p=0.09), severity of lesion by 31% (p=0.13), and average number of necrotic cores per arterial tree by 39% (p=0.35) compared to mice fed the regular diet.…

Read more: Nutrient supplementation modulates angiotensin II-mediated atherosclerosis in ApoE KO mice

Evolution of angiotensin II-mediated atherosclerosis in ApoE KO mice

J. Cha, V. Ivanov, S. Ivanova, T. Kalinovsky, M. Rath, A. Niedzwiecki

Molecular Medicine Reports, 2010, 3:565-570

Abstract
The dysregulation of renin-angiotensin system signaling is a contributing factor to the development of atherosclerosis and cardiovascular disease. We studied a progression of angiotensin II (AngII)-induced arterial wall atherosclerosis after its induction. Atherosclerosis was accelerated in ApoE (-/-) C57B6 mice by 4 weeks of continuous osmotic pump administration of AngII at 23 nmol/24 h. Changes in aortae were evaluated at 4 and 16 weeks after pump installation, as well as in mice without AngII administration. AngII supplementation induced additional lesions in the aortic arch and its vessels 4 weeks after pump installation showing that AngII had taken effect in comparison to non-AngII controls.…

Read more: Evolution of angiotensin II-mediated atherosclerosis in ApoE KO mice

Plant-Derived Micronutrients Suppress Monocyte Ahesion to Cultured Human Aortic Endothelial Cell Layer by Modulating Its Extracellular Matrix Composition

V. Ivanov, S. Ivanova, T. Kalinovsky, A. Niedzwiecki, M. Rath
Journal of Cardiovascular Pharmacology 2008, 52: 55-65

Abstract
Monocyte adhesion to endothelium plays an important role in atherosclerosis. We investigated the effects of micronutrients on monocyte-binding properties of extracellular matrix (ECM) produced by human aortic endothelial cells (AoEC). Confluent cultures of AoEC were exposed to ascorbic acid, quercetin, gotu kola extract (10% asiatic acid), green tea extract (40% epigallocatechin gallate), or a mixture of these micronutrients for 48 hourss. AoEC-produced ECM was exposed by differential treatment. U937 monocyte adhesion was assayed by fluorescence. ECM composition was assayed immunochemically and with radiolabeled metabolic precursors. AoEC exposure to micronutrients reduced ECM capacity to bind monocytes in a dose-dependent manner.…

Read more: Plant-Derived Micronutrients Suppress Monocyte Ahesion to Cultured Human Aortic Endothelial Cell Layer by Modulating Its Extracellular Matrix Composition

Anti-Atherogenic Effects of a Mixture of Ascorbic Acid, Lysine, Proline, Arginine, Cysteine, and Green Tea Phenolics in Human Aortic Smooth Muscle Cells

V. Ivanov, M.W. Roomi, T. Kalinovsky, A. Niedzwiecki, M. Rath
Journal of Cardiovascular Pharmacology 2007, 49(3): 140-145.

Certain drastic behavioral modifications by arterial wall smooth muscle cells (SMC) have been considered key steps in the formation of atherosclerotic lesions: massive migration of SMC from the media to the intima layer of the vessel, dedifferentiation of SMC to proliferating phenotype, and increased secretion of inflammatory cytokines as a response to inflammatory stimuli. We investigated the anti-atherogenic effects of naturally occuring compounds (ascorbic acid, green tea extract, lysine, proline, arginine, and N-acetyl cysteine) using the model of cultured aortic SMC. Cell growth was measured by DNA synthesis, cell invasiveness was measured through Matrigel, matrix metalloproteinase-2 (MMP-2) secretion was measured by zymography, and SMC secretion of monocyte chemoattractant protein-1 (MCP-1) and interleukin-6 (IL-6) was measured by immunochemistry. Fetal bovine serum-stimulated SMC growth was inhibited by the nutrient mixture (NM) with 85% inhibition at 100 µg/mL.…

Read more: Anti-Atherogenic Effects of a Mixture of Ascorbic Acid, Lysine, Proline, Arginine, Cysteine, and Green Tea Phenolics in Human Aortic Smooth Muscle Cells

Extracellular Matrix-Mediated Control of Aortic Smooth Muscle Growth and Migration by a Combination of Ascorbic Acid, Lysine, Proline, and Catechins

V. Ivanov, S. Ivanova, M.W. Roomi, T. Kalinovsky, A. Niedzwiecki, M. Rath
Journal of Cardiovascular Pharmacology 2007, 50(5): 541-547

Extracellular matrix (ECM) function and structure are severely compromised at atherosclerotic lesion sites, contributing to initiation and progression of the disease. This study investigated whether ECM biological properties would be beneficially affected by exposure to nutrients essential for collagen synthesis and posttranslational modification. Confluent layers of human aortic smooth muscle cells (SMC) grown on collagen substrate were cultured in the presence of the tested compounds for 7 to 10 days. Pretreated cells were removed from the ECM surface by differential treatment and replaced with secondary innocent SMC cultures.…

Read more: Extracellular Matrix-Mediated Control of Aortic Smooth Muscle Growth and Migration by a Combination of Ascorbic Acid, Lysine, Proline, and Catechins

Enhancement of Cardio-Protective Effects and Attenuation of Adverse Effects of Female Sex Hormones on Cultured Human Vascular Smooth Muscle Cells by a Combination of Ascorbic Acid, Lysine, Proline, Arginine, Cysteine, and Epigallocatechin Gallate

V.Ivanov, S. Ivanova, W. Roomi, T.Kalinovsky, A. Niedzwiecki, M.Rath
Journal of the American Neutraceutical Association 2005, 8(1): 46-51

In this in vitro study, the effects of adjunctive use of a formulation containing ascorbic acid, lysine, proline, arginine, N-acetyl cysteine, and epigallocatechin gallate (NS) with female sex hormones was tested on human aortic smooth muscle cells (SMC). Estradiol and progesterone stimulated DNA synthesis in SMC 30% and 24% respectively at 25-150 nmol/L concentrations. NS (20 µg/ml) inhibited SMC growth by 30% over the control and reversed the stimulatory effect of the sex hormones to a maximum of 25% inhibition. Dehydroepiandrosterone sulfate (DHEAS) inhibited SMC growth by 50% at 0.1 mmol/L. Addition of NS enhanced the DHEAS inhibitory effect to 70% as compared to the control.…

Read more: Enhancement of Cardio-Protective Effects and Attenuation of Adverse Effects of Female Sex Hormones on Cultured Human Vascular Smooth Muscle Cells by a Combination of Ascorbic Acid, Lysine, Proline, Arginine, Cysteine, and Epigallocatechin Gallate

Reduction in the Frequency of Arrhythmic Episodes in Patients with Paroxysmal Atrial Arrhythmia with a Vitamin/Essential Nutrient Program

A. Niedzwiecki, T. Kalinovsky, M. Rath
Journal of the American Neutraceutical Association 2005, 8(3): 19-25

Introduction:
Chronic deficiency of vitamins and other essential nutrients impairs cellular bio-energy production and can lead to disturbances in the generation and conduction of electrical impulses in the myocardium. We investigated the effect of long-term supplementation with a combination of vitamins and other essential nutrients on the number of clinically apparent episodes in patients with paroxysmal atrial arrhythmia.…

Read more: Reduction in the Frequency of Arrhythmic Episodes in Patients with Paroxysmal Atrial Arrhythmia with a Vitamin/Essential Nutrient Program

Bioflavonoids Effectively Inhibit Smooth Muscle Cell-Mediated Contraction of Collagen Matrix Induced by Angiotensin II

V. Ivanov, M.W. Roomi, T. Kalinovsky, A. Niedzwiecki, M. Rath
The Journal of Cardiovascular Pharmacology 2005, 46(5): 570-6

Introduction:
Plant-derived bioflavonoids have been recognized to support arterial wall structural integrity and interfere with a variety of pro-atherosclerotic stimuli. In this study we tested the effects of bioflavonoids on the contractile activity of cultured human aortic smooth muscle cells (SMC) embedded in a three-dimensional type I collagen matrix.…

Read more: Bioflavonoids Effectively Inhibit Smooth Muscle Cell-Mediated Contraction of Collagen Matrix Induced by Angiotensin II

A Nutrient Mixture Containing Ascorbic Acid, Lysine, Proline, Arginine, Cysteine, and Green Tea Extract Suppresses Autocrine Inflammatory Response in Cultured Human Aortic Smooth Muscle Cells

V. Ivanov, S. Ivanova, M.W. Roomi, T. Kalinovsky, A. Niedzwiecki, M. Rath
Research Communications in Molecular Pathology and Pharmacology 2004

Introduction:
Recognition of the involvement of inflammatory processes in atherosclerotic lesion initiation and development of pathological consequences initiated a search for an effective inhibitor. Naturally occurring compounds demonstrate a wider spectrum of biological activity and fewer side effects than synthetic drugs. Mixtures of natural compounds often produce synergistically enhanced therapeutic action.…

Read more: A Nutrient Mixture Containing Ascorbic Acid, Lysine, Proline, Arginine, Cysteine, and Green Tea Extract Suppresses Autocrine Inflammatory Response in Cultured Human Aortic Smooth Muscle Cells