INFLUENCE OF ANTHROPOGENIC FACTORS ON

THE CVSMECHANISMS OF ACTION OF

POLLUTANTS ON MYOCARDIUM AND VESSELS

VISITH DANTANARAYANA

201

INTRODUCTION

WHAT ARE ANTHROPOGENIC FACTORS?

The term "anthropogenic" means of, relating to, or involving the impact of humans on nature.

OUR FOCUS

CARDIOVASCULAR DISEASE

Cardiovascular disease is a class of diseases that involve the heart, the blood vessels (arteries, capillaries, and veins) or both.

CAUSES

• There are several risk factors for heart diseases: age, gender, tobacco use, physical inactivity, excessive alcohol consumption, unhealthy diet, obesity, family history of cardiovascular disease, raised blood pressure (hypertension), raised blood sugar (diabetes mellitus), raised blood cholesterol (hyperlipidemia), psychosocial factors, poverty and low educational status, and AIR POLLUTION.

HOW AIR POLLUTION CAUSES CVD RISK?

• PARTICULATE MATTER has been studied for its short- and long-term exposure effects on cardiovascular disease.

ATMOSPHERIC PARTICULATE MATTER – ALSO KNOWN AS PARTICULATE MATTER (PM) OR PARTICULATES – IS MICROSCOPIC SOLID OR LIQUID MATTER SUSPENDED IN THE EARTH'S ATMOSPHERE.

SUBTYPES INCLUDE: SUSPENDED PARTICULATE MATTER, RESPIRABLE SUSPENDED PARTICULATE MATTER (DIAMETER OF 10µM OR LESS) ANDULTRAFINE PARTICLES (DIAMETER OF 2µM OR LESS).

SOURCES OF PARTICULATE MATTER

• Some particulates occur naturally, originating from volcanoes, dust storms, forest and

grassland fires, living vegetation, and sea spray.

• Human activities, such as the burning of fossil fuels in vehicles, power plants and various industrial processes also generate significant amounts of particulates – ANTHROPOGENIC AEROSOLS—those made by human activities—currently account for about 10 % of the total mass of aerosols in our atmosphere.

COMPOSITION

• DEPENDS ON THE SOURCE.

• Wind-blown mineral dust tends to be made of MINERAL OXIDES.

• SECONDARY PARTICLES ORIGINATE FROM THE OXIDATION OF PRIMARY GASES RELEASED AS ANTHROPOGENIC FACTORS ( SULPHUR…ETC).

• ORGANIC PARTICLES CAN BE OF BOTH PRIMARY AND SECONDARY PARTICLES.

PATHWAYS OF INFILTRATION

CLASSICAL PATHWAYINDIRECT PULMONARYDERIVED EFFECTS

ALTERNATE PATHWAYDIRECT TRANSLOCATIONINTO THE CIRCULATION

CLASSICAL PATHWAY

THE HYPOTHESIS PROPOSES THAT INHALATION OF PARTICULATE MATERIAL LEADS TO PULMONARY INFLAMMATION WHICH RELEASES BOTH PROTHROMBOTIC AND INFLAMMATORY CYTOKINES INTO THE CIRCULATION THAT COULD SUBSEQUENTLY RESULT IN CVD. EXPOSURE TO SUCH ENVIRONMENTS WITH AMBIENT PARTICULATE MATERIAL TRIGGERS THE ELEVATED CONCENTRATION OF CYTOKINES. SUCH AS: INTERLEUKINS (1-α AND 6) AND GRANULOCYTE –MACROPHAGE COLONY STIMULATING FACTOR.

ALTERNATE PATHWAY

• This hypothesis proposes that inhaled, insoluble, fine PM or nanoparticles could rapidly translocate into the circulation, with the potential for direct effects on hemostasis and cardiovascular integrity.

• The ability of nanoparticles to cross the lung–blood barrier is likely to be influenced by a number of factors including particle size and charge, chemical composition, and propensity to form aggregates.

DIRECT TRANSLOCATION INTO THE CIRCULATION

• Once in the circulation, nanoparticles could interact with the vascular endothelium or have direct effects on atherosclerotic plaques and cause local oxidative stress and proinflammatory effects similar to those seen in the lungs. Increased inflammation could destabilize coronary plaques, which might result in rupture, thrombosis, and acute coronary syndrome.

(A) Classical and alternative pathways through which combustion-derived nanoparticulate matter induces cardiovascular effects.

(B) Transmission electron micrograph of the alveolar-duct–terminal bronchiolar region that demonstrates the close proximity between the alveolar wall and capillary network.

MECHANISMS OF THE ADVERSE EFFECTS

UNDER THIS TOPIC THREE MAIN MECHANISMS WOULD BE PRIORITIZED. THEY ARE:

1. ARTHEROGENESIS

2. ARTHEROTHROMBOSIS

3. ARRYTHMOGENESIS

ARTHEROGENESIS

Repeated exposure to air pollution could plausibly induce vascular inflammation, oxidative stress, and promote ATHEROSCLEROTIC PLAQUE EXPANSION or rupture.

ARTHEROGENESIS

• IN A CROSS-SECTIONAL, POPULATION-BASED STUDY, KÜNZLI AND COLLEAGUES EXAMINED CAROTID INTIMA–MEDIA THICKNESS MEASUREMENTS IN NEARLY 800 RESIDENTS OF LOS ANGELES, CA. PERSONAL AIR POLLUTION EXPOSURES WERE ESTIMATED WITH A GEOSTATISTICAL MODEL THAT MAPPED THEIR AREA OF RESIDENCE TO PM VALUES RECORDED BY LOCAL POLLUTION-MONITORING STATIONS.

• FOR EVERY 10 G/M3 INCREASE IN PM2.5, CAROTID INTIMA–MEDIA THICKNESS INCREASED BY 6%, A FIGURE WHICH FELL TO 4% AFTER ADJUSTMENT FOR POTENTIAL CONFOUNDING VARIABLES.

APOLIPOPROTEIN E KNOCK-OUT MICE

PROLONGED EXPOSURE TO CONCENTRATED AMBIENT PM2.5 INCREASES AORTIC PLAQUE AREA AND BURDEN, WHEN COMPARED WITH FILTERED AIR, IN APOLIPOPROTEIN-E-KNOCKOUT MICE FED A HIGH-FAT DIET.

ARTHEROTHROMBOSIS

ATHEROTHROMBOSIS IS CHARACTERIZED BY DISRUPTION OF AN ATHEROSCLEROTIC PLAQUE AND THROMBUS FORMATION, AND IS THE MAJOR CAUSE OF ACUTE CORONARY SYNDROMES AND CARDIOVASCULAR DEATH.

UNDER THIS TOPIC WE WILL FOCUS ON TWO ASPECTS: THEY ARE –THROMBOSIS

VASCULAR DYSFUNCTION

THROMBOSIS

VASCULAR DYSFUNCTION

OBSERVATIONAL CLINICAL STUDIES HAVE PROVEN THAT OVER EXPOSURE TO PARTICULATE MATTER IN THE AIR ARE LIKELY TO CAUSE INCREASED VASOCONSTRICTION AND REDUCE THE TENDENCY OF ENDOTHELIUM DEPENDENT VASODILATION.

THEY ACT BY INHIBITING THE PRODUCTION OF NITRIC OXIDE.

L-Arginine is metabolized in endothelial cells viaendothelial nitric oxide synthase to nitric oxide,which then acts downstream to reduce plateletadhesion, decrease leukocyte adhesion, inhibit smooth muscle proliferation and migration, andinduce vasodilation.

ARRYTHMOGENESIS

• SOME INVESTIGATORS HAVE POSTULATED THAT DEPOSITED PARTICLES COULD STIMULATE IRRITANT RECEPTORS IN THE AIRWAYS AND DIRECTLY INFLUENCE HEART RATE AND RHYTHM VIA REFLEX ACTIVATION OF THE NERVOUS SYSTEM.

• OVERALL, THE PROARRHYTHMIC POTENTIAL OF AIR POLLUTION REMAINS UNCERTAIN AND HAS YET TO BE DEFINITIVELY ESTABLISHED.

MECHANISMS OF DISEASE