The Role of Chronic Inflammation in Cardiovascular Disease ...

1 Page 32 Alternative Medicine Review Volume 9, Number 1 2004 Cardiovascular / Inflammation ReviewCopyright 2004 Thorne Research, Inc. All Rights Reserved. No Reprint Without Written PermissionAbstractMultiple risk markers for atherosclerosis andcardiovascular Disease act in a synergistic waythrough inflammatory pathways. This articlediscusses some of the key inflammatorybiochemical risk markers for cardiovasculardisease.

2 In particular, the role of three basiccell types affected by these risk markers(endothelial cells, smooth muscle cells, andimmune cells), the crucial role of inflammatorymediators, nitric oxide balance incardiovascular pathology, and the use ofnutrients to circumvent several of theseinflammatory risk markers for Cardiovascular diseasehave a pro-inflammatory component, whichstimulates the release of a number of activemolecules such as inflammatory mediators,reactive oxygen species, nitric oxide, andperoxynitrite from endothelial, vascular smoothmuscle.

3 And immune cells in response to oxide plays a pivotal role in preventingthe progression of atherosclerosis through itsability to induce vasodilation, suppressvascular smooth muscle proliferation, andreduce vascular lesion formation. Nutrientssuch as arginine, antioxidants (vitamins C andE, lipoic acid, glutathione), and enzymecofactors (vitamins B2 and B3, folate, andtetrahydrobiopterin) help to elevate nitric oxidelevels and may play an important role in themanagement of Cardiovascular Disease .

4 Otherdietary components such as DHA/EPA fromfish oil, tocotrienols, vitamins B6 and B12, andquercetin contribute further to mitigating theinflammatory process.(Altern Med Rev 2004;9(1):32-53)The Role of Chronic Inflammation inCardiovascular Disease andits Regulation by NutrientsHenry Osiecki, BSc (Hons), Grad Dip Nutr & DieteticsIntroductionMultiple risk factors for atherosclerosisand Cardiovascular Disease include disordered lipidprofiles, autoimmunity, infection, homocysteine,asymmetrical dimethylarginine, C-reactive pro-tein, genetic predisposition, and various Many risk factors act in a coordinatedor synergistic way through one or two inflamma-tory pathways.

5 Risk factors appear to act on threecell types that coordinate their action to influencecardiovascular dynamics, function, and cell types include: Endothelial cells that line the vascularlumen. They control the intra- andtranscellular flow of nutrients, hormones,and immune cells, and regulate vasculartone and blood Smooth muscle cells (SMC) or vascularsmooth muscle cells (VSMC) thatmaintain vascular tone and structure. Immune cells, including monocytes/macrophages and T lymphocytes, whichdefend the endothelium and SMC fromchemical and biological disruption or over-expression of thecoordinated activities of these cells can lead tocardiovascular Chronic inflammationHenry Osiecki BSc(Hons), Post Grad.

6 Dip. Nutrition &Dietetics author Cancer: A Nutritional BiochemicalApproach, 2003; nutritional consultant to nutritional/pharmaceutical address: Bioconcepts, 9/783 KingsfordSmith Dve, Eagle Farm 4009 AustraliaCopyright 2004 Thorne Research, Inc. All Rights Reserved. No Reprint Without Written PermissionAlternative Medicine Review Volume 9, Number 1 2004 Page 33 Review Cardiovascular / Inflammationis the most common disruptor of the activities ofthese cells.

7 Risk factors for Cardiovascular diseasethat have a pro-inflammatory component includeLDL cholesterol, smoking, elevated blood sugar,hypertension, diabetes, infection, homocysteine,ischemia, oxidant damage, interleukin-6, lipopro-tein (a), high sensitivity C-reactive protein (hs-CRP), serum intracellular adhesion molecule-1,and ,4,5,11-14 In addition, these in-flammatory risk markers can react synergisticallyto increase relative risk (Figure 1). One commonlink among these risk factors is the activity andmetabolism of nitric oxide (NO).

8 Endothelial Cell FunctionEndothelial cells play a vital physiologi-cal role in dividing blood from tissue. These cellsactively inhibit the activation of the hemostaticmechanism and maintain blood circulation andfluidity, limit the efflux of cells and protein fromthe bloodstream, and participate in the mainte-nance of normal vasomotor cells are highly metabolicallyactive and behave in a similar manner to paracrineor endocrine gland cells in the release of chemi-cal ,15,16 The endothelium generates anumber of active molecules in response to injuryor toxic chemical or oxidant stimuli.

9 Such as: Adhesion molecules, intracellularadhesion molecule (ICAM-1), vascularcell adhesion molecule (VCAM-1),fibronectin, selectins, interleukin-1,heparin sulfate17 Clotting or coagulation factors17,18 (vonWillebrand Factor, thromboxane,prostacyclin) Fibrinolysis factors19,20 ( , tissueplasminogen factor)Figure 1. Relative and Synergistic Risk among Several Associated FactorsLipoprotein(a)HomocysteineTotal CholesterolLDL-CholesterolApolipoprotein BTC:HDL-C Ratiohs-CRPhs-CRP + TC:HDL-C RatioRelative Risk of Cardiovascular Events According To Several Biochemical MarkersRisk risk for future Cardiovascular events among apparently healthy women in the Women's Health Study according to baseline values of Lipoprotein(a), Homocysteine, LDL-Cholesterol, Apolipoprotein B, high-sensitivity C-Reactive Protein (hs-CRP) and TC:HDL-Cholesterol (TC.)

10 HDL-C ) consistency, risk estimates and 95% C's are computed for those in the top quartile, as opposed to the bottom quartile, for each 34 Alternative Medicine Review Volume 9, Number 1 2004 Cardiovascular / Inflammation ReviewCopyright 2004 Thorne Research, Inc. All Rights Reserved. No Reprint Without Written Permission Components of the renin-angiotensinsystem21 ( , angiotensin II that acts as apro-inflammatory cytokine and augmentsthe production of reactive oxygen species) Prostaglandins22-24 ( , prostacyclin) Growth-promoting or angiogenesis factors(transforming growth factor-beta (TGF- ),platelet-derived growth factor (PDGF))25 Vascular tone regulators18,25-28 (NO andendothelin-1)