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             Endothelial	dysfunction	and	
             oxidative	stress
             Dr	Craige	Golding
             MBCHB	(cum	laude),	FCP(SA)	:	Fellow	of	the	College	of	Physicians	of	South	Africa
             ABAARM :American Academy Board Certified in Antiaging and Regenerative Medicine
             FAAFM	:	Fellowship	in	Antiaging	and	Functional	Medicine




              T
                    he	 various	 forms	 of	 athero-         As	 we	 age,	 some	 of	 the	 special-     endothelial	 lesion.	 Fibrinogen	 may	
                    sclerosis,	 including	 coronary	      ized	 functions	 of	 the	 endothelium	      contribute	to	plaque	buildup	or	par-
                    thrombosis,	 stroke	 and	 pe-         become	blunted.					The	self	renewal	       ticipate	in	blood	clot-induced	block-
             ripheral	arterial	disease,	continues	        process	 weakens,	 the	 endothelial	        age	 of	 an	 artery	 after	 an	 unstable	
             to	 be	 the	 leading	 cause	 of	 death	      barrier	 becomes	 leaky	 and	 signals	      atherosclerotic	plaque	ruptures.30
             worldwide.						Black	Africans	are	to-       to	 the	 middle	 wall	 smooth	 muscle	        Glucose	 at	 even	 high-normal	
             day	too	suffering	from	an	increased	         cells	 that	 regulate	 their	 function	     levels	 may	 accelerate	 the	 glyca-
             incidence	of	cardiovascular	disease	         become	altered.	The	vascular	aging	         tion	 process	 that	 causes	 arterial	
             due	 to	 the	 adoption	 of	 a	 western	      process	and	atherosclerosis	become	         stiffening,	while	high-normal	fasting	
             lifestyle	and	diet.                          intertwined	as	we	age.                      insulin inflicts direct damage to the
               The	 endothelium	 (the	 largest	                                                       endothelium.31-36
             organ	in	the	body)	controls	vascular	        The	arterial	wall	under	                      High	 levels	 of	 iron	 promote	 LDL	
             smooth	 muscle	 tone	 by	 secreting	         attack	(excerpt	lef	October	                oxidation	 in	 the	 damaged	 endothe-
             relaxing	 and	 contracting	 fac-             2005)                                       lium,	 while	 low	 levels	 of	 testoster-
             tors.					There	is	a	constant	release	       High	 blood	 pressure,	 elevated	 LDL	      one	appear	to	interfere	with	normal	
             of	 endothelium-derived	 relaxing	           and	 triglycerides,	 cigarette	 smok-       endothelial	function.9,11,14
             factors	 (EDRFs),	 whose	 biologic	          ing,	 diabetes,	 obesity,	 and	 lack	 of	     C-reactive	 protein	 is	 not	 only	
             activity	 is	 provided	 by	 nitric	 oxide	   exercise	 contribute	 to	 endothelial	      an inflammatory marker, but also
             (or	 similar	 molecules)	 and	 con-          dysfunction	and	the	subsequent	de-          directly	 damages	 the	 endothelium.	
             stantly	counteracts	vasoconstrictor	         velopment	of	atherosclerosis.15-25          Chronic inflammation, as evidenced
             substances	 such	 as	 noradrenaline,	          Additional	 endothelial-damaging	         by	 persistent	 high	 levels	 of	 C-reac-
             angiotensin	 II	 or	 endothelin	 I.	 The	    factors	include	excess	levels	of	glu-       tive	protein,	creates	initial	injuries	
             normal	 functioning	 endothelium	            cose,	 insulin,	 iron,	 homocysteine,	      to	 the	 endothelium	 and	 also	 ac-
             is	 able	 to	 increase	 the	 release	 of	    fibrinogen, and C-reactive protein,         celerates	the	progression	of	existing	
             EDRFs	 in	 response	 to	 physiological	      as	 well	 as	 low	 HDL	 and	 free	 testo-   atherosclerotic	lesions.3,27
             stimuli,	such	as	the	stress	exerted	         sterone	(in	men).3,9,10,24,26-28              In	response	to	numerous	published	
             by	 the	 circulating	 blood,	 or	 to	          Homocysteine	 is	 particularly	 dan-      studies,	health-conscious	people	are	
             humoral	 stimulation	 by	 vasoactive	        gerous	 because	 it	 can	 induce	 the	      altering	 their	 diets,	 taking	 drugs,	
             substances	such	as	acetylcholine	or	         initial	 injury	 to	 the	 endothelium.	     hormones,	and	dietary	supplements,	
             bradykinin.	 The	 endothelium	 is	 in	       Homocysteine	then	facilitates	oxida-        and	trying	to	exercise	regularly	in	or-
             effect	both	a	target	and	a	modula-           tion	of	the	fat/LDL	that	accumulates	       der	to	reduce	these	atherosclerosis	
             tor	 of	 blood	 pressure-related	 and	       beneath	the	damaged	endothelium,	           risk	factors.	However,	these	efforts	
             hormonal influences.                         and finally contributes to the abnor-       alone	cannot	be	completely	success-
               Normal	 functions	 of	 endothelial	        mal	 accumulation	 of	 blood	 compo-        ful	because	age	itself	is	a	major	risk	
             cells	include	mediation	of	coagula-          nents	 around	 the	 atherosclerotic	        factor	for	atherosclerosis.
             tion,	 platelet	 adhesion,	 immune	          lesion.29                                     Atherosclerotic	 risk	 conferred	 by	
             function,	 control	 of	 volume	 and	           Fibrinogen	 is	 a	 clotting	 factor	      age	is	attributable	in	large	measure	
             electrolyte	content	of	the	intravas-         that	accumulates	at	the	site	of	the	        to	pathological	endothelial	dysfunc-
             cular	and	extravascular	spaces.                                                          tion.37,38	As	noted	earlier,	endothelial	

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Update Mar article 14 - Solal - 1 1                                                                                                   2009/02/19 10:07:54 AM
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             dysfunction	is	not	synonymous	with	         mute	for	a	long	time	and	frequently	         were	not	diagnosed	with	the	condi-
             atherosclerosis,	 but	 the	 two	 proc-      manifests	 itself	 with	 an	 acute	 car-     tion,	and	beta-carotene	levels	were	
             esses	 are	 increasingly	 intertwined	      diovascular	 event;	 therefore,	 the	        less	 than	 a	 third	 of	 those	 without	
             with	advancing	age.	                        possibility	 of	 detecting	 the	 disease	    atherosclerosis.
                                                         in	 a	 subclinical	 phase	 and	 reducing	      Oxidative	stress	resulting	from	the	
             Endothelial	dysfunction	                    or	 reversing	 its	 progression	 is	 an	     oxidation	of	low-density	lipoprotein	
             markers:                                    issue	 of	 relevance,”	 the	 authors	        (LDL)	cholesterol	in	the	wall	of	the	
             1.	VEGF	(Vascular	endothelial	              write.	 “Antioxidants,	 which	 may	          artery results in inflammation which
                 growth	factor)                          inhibit	 lipid	 peroxidation,	 could	        stimulates	the	differentiation	of	im-
             2.	ADMA	(Asymmetric	dimethyl-               play	 an	 important	 protective	 role	       mune	system	cells	called	monocytes	
                 arginine)                               against	 the	 formation	 of	 simple	         into	 macrophages.	 Macrophages	
             3.	VCAM-1	(vascular	cell	adhesion           and	 complex	 atherosclerotic	 le-           accumulate	 lipids	 to	 form	 foam	
                 molecules)                              sions,	 which	 progressively	 protrude	      cells	which	thicken	the	walls	of	the	
             4.	NOS	(Nitric	oxide	synthase)              into	 the	 arterial	 lumen,	 causing	        artery.	 Antioxidants	 such	 as	 those	
               ADMA	is	involved	in	the	pathogen-         stenosis	 or	 occlusion.	 In	 particular,	   evaluated	in	the	current	study	could	
             esis	of	hypertension	and	atheroscle-        increased	 carotid	 intima-media	            help	protect	against	this	process	by	
             rosis	 through	 its	 inhibition	 of	 the	   thickness	represents	an	early	phase	         preventing	LDL	oxidation.
             formation	of	the	endogenous	vascu-          of	the	atherosclerotic	process	and	is	         “Regular	 intake	 of	 foods	 rich	 in	
             loprotective	 molecule,	 nitric	 oxide	     widely	used	as	a	marker	of	subclini-         lycopene	 and	 other	 antioxidant	
             (NO).	 Determination	 of	 ADMA	 can	        cal	atherosclerosis	which	correlates	        vitamins	 may	 slow	 the	 progression	
             thus	help	to	predict	both	the	likeli-       with	 established	 coronary	 heart	          of	 atherosclerotic	 processes	 and	
             hood	 of	 developing	 cardiovascular	       disease.”                                    modify	 the	 early	 stages	 of	 athero-
             disease	 and	 its	 prognosis.	 A	 new	        Two	 hundred	 and	 twenty	 men	            sclerosis,	with	a	consequent	reduc-
             competitive	ELISA	test	for	ADMA	is	a	       and	 women	 between	 the	 ages	 of	          tion	 in	 cardiovascular	 events,”	 the	
             useful	and	fully	validated	tool	suit-       45	 and	 65	 without	 history	 of	 tran-     authors	conclude.
             able	for	routine	laboratory	use.            sient	 ischemic	 attack,	 stroke,	 or	
               Available	tests	to	detect	endothe-        other	 conditions	 related	 to	 carotid	     Oxidative stress profile
             lial	 dysfunction	 in	 South	 Africa	       artery	disease	were	enrolled	at	the	         (blood)
             include	:                                   San	 Camillo	 de	 Lellis	 Hospital,	 in	     1.	Malondialdehyde
             a)	Ultra	sensitive	CRP                      Manfredonia,	 Italy.	 Participants	          2.	Glutathione
             b)	Von	Willebrand	Factor	(WF)	              underwent	 ultrasonographic	 evalu-          3.	CoEnzyme	Q10
             c)	PAI-1	(Plasminogen	activator             ation	 of	 the	 extracranial	 carotid	       4.	Vitamin	C
                 inhibitor-1)	                           arteries,	 and	 blood	 samples	 were	        5.	b-Carotene	(including	cryptoxan-
             d)	FDP	(Fibrinogen	degradation	             analysed	 for	 lipids,	 C-reactive	 pro-        thin	and	lycopene)
                 products)	–	as	D-dimer                  tein	and	other	factors,	in	addition	to	
                                                         plasma	levels	of	vitamin	A,	vitamin	         RefeRences :
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             g)	Active	renin                               One hundred and twenty-five par-           Neurol. 2004 Sep;17(3):148-56.
                                                         ticipants	were	found	to	have	carotid	        2. Toner I, Peden CJ, Hamid SK, et al. Magnetic resonance
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                 enzyme)                                 0.8	millimeters	or	more.	Body	mass	          cysteine predicts progression of atherosclerosis. Atherosclerosis.
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Update Mar article 14 - Solal - 2 2                                                                                                                        2009/02/19 10:07:57 AM
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