HSCI 560 Exam 2: Cardiovascular Toxicity

• creatine kinase

• myoglobin

• BNP

• CRP

• cardiac troponins

what are the 5 biomarkers for cardiac toxicity

Myocardial structural injury

What do all cardiac toxicity biomarkers indicate?

Lack of specificity — many markers also appear in non-cardiac tissues.

What is a major limitation of current cardiac biomarkers?

nothing about cardiac damage

What does an increase in CK-BB indicate?

possible cardiac damage, but not specific or sure

What does an increase in CK-MM suggest?

Cardiac toxicity — more specific for myocardial injury.

What does an increase in CK-MB indicate?

An enzyme released from damaged muscle; three isoforms:

• CK-BB (brain/kidney)

• CK-MM (skeletal muscle/myocardium)

• CK-MB (myocardium/some skeletal muscle)

What is Creatine Kinase (CK) and how many isoforms exist?

myoglobin

The following characteristics are found in which biomarker?

• Found in all muscle types

• Serum levels are rapidly increased after myocardial

injury (peak 1-4h)

B-type Natriuretic Peptide (BNP)

The following characteristics are found in which biomarker?

• Marker of Heart Failure

• Cardiac neurohormone secreted by the ventricular

myocardium and correlates to ventricular wall tension 27

C-Reactive Protein (CRP)

The following characteristics are found in which biomarker?

• Correlated w/many things, but usually indicative of smth bad

• Acute phase protein

• Marker of systemic and vascular inflammation so it’s supplemental

• Appears to be predictive of future adverse cardiac events (not specific)

cardiac troponins

The following characteristics are found in which biomarker?

• Best biomarker bc it’s very specific to the heart

• Irreversible damage has alr occurred if seen

• “gold standard” for diagnosis of acute myocardial infarction and also of cocaine-induced cardiac damage

• cTnT and cTnI are myofilament constituents (exclusive to

  cardiomyocytes)

It’s involved in counter-regulation, not directly in injury, making interpretation complex.

Why is BNP considered poorly understood as a biomarker?

No way to stop toxicity once biomarkers rise — detection occurs after damage.

What is a key disadvantage of current cardiac biomarkers?

biomarkers

We need more sensitive and early ________ to detect cardiac injury before irreversible damage.

smoking

what increase the risk of cardiovasuclar outcomes

heart cannot metabolize acetaldehyde

Why is the heart especially sensitive to alcohol toxicity?

calcium

metals disrupt cardiac function by disrupting what

Cadmium, Lead, Cobalt

what metals disrupt intracellular Calcium regulation

Nickel, Manganese, Lanthanum

what metals “lock in” Calcium channels

Endothelial Nitric Oxide Synthase (eNOS) — produces basal levels of NO for normal vessel tone.

What is the normal (basal) enzyme responsible for nitric oxide production in vessels?

vessel constrction (vasoconstriction)

exposure that disrupts normal eNOS lvls causes what

induce iNOS to produce more NO in an attempt to restore vasodilation

what is the body’s response to reduced NO activity and vasoconstriction

Stimulates smooth muscle relaxation, leading to vasodilation and improved blood flow.

What is the overall role of NO in vascular physiology?

vascular effects

(iNOS) is often is used as a marker of what following exposure

NO

release of what can stimulate relaxation

ET-1

potent vasoconstrictor peptide produced by endothelial cells.

• Toxic exposures (chemicals, oxidative stress, pollutants, etc.)

• Inflammatory stimuli

These stressors cause endothelial cells to release ET-1, which acts on the surrounding smooth muscle.

What triggers ET-1 release?

stimulate smooth muscle contraction, causing vasoconstriction.

What is ET-1’s main function?

A: Cigarette smoke reduces NO production and bioavailability by:

• Damaging endothelial cells (which make NO via eNOS)

• Increasing oxidative stress, which destroys existing NO molecules

• Inhibiting eNOS activity

How does cigarette smoke affect nitric oxide (NO)?

vascular smooth muscle cannot relax, leading to vasoconstriction (narrowing of blood vessels).

What happens when NO levels decrease?

vasorelaxation

what is required for an erection

smoking cigarettes releases ROS and other compounds that can damage endothelial cells, disrupting eNOS lvls. then, we see a reduced lvl of NO, leading to vasoconstriction. vasorelaxation is needed to have an erection

how are smoking cigarettes and erectile dysfunction related

Viagra

selective inhibitor of phosphodiesterase type 5 (PDE5).

• Normally, NO stimulates guanylyl cyclase → makes cyclic GMP (cGMP) → smooth muscle relaxes → blood flows into erectile tissue.

• PDE5 breaks down cGMP, ending the erection.

• Viagra inhibits PDE5, so cGMP is not broken down, leading to higher cGMP levels, prolonged relaxation, and sustained erection

How does Viagra help produce or maintain an erection?

• Both Viagra and nitrates increase NO–cGMP signaling, causing vasodilation.

• When combined, they dramatically lower blood pressure → can cause severe hypotension, syncope, or cardiac ischemia.

Why can’t Viagra be prescribed with nitrates (like nitroglycerin)

PDE5

an enzyme that breaks down cyclic GMP (cGMP) into inactive GMP