Exercise for Cardiovascular Disease Prevention and Treatment From Molecular to Clinical, Part 1

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transport, maintenance of barrier function and permeability), smooth muscle cells

(responsible for peripheral resistance to blood flow generated by the beating heart

and regulation of blood pressure), cardiac mast cells (store and release a variety of

biologically active mediators), cardiac macrophages (functioning in remodeling,

wound healing and regeneration) [ 43 , 49 – 54 ], all of which rely on redox reactions

and redox signaling messengers to send physiological inputs to perform these fun-

damental processes.

While, the redox homeostasis is a precise balance between the endogenous levels

of oxidants and antioxidants, in today’s situation our human system is persistently

challenged to maintain it due to continuous fluctuations in the environment, dietary

styles, exposure to toxic chemicals coupled with less physical activity, chronic stress

and other unhealthy lifestyle choices. In addition, heart being a vital organ abundant

in mitochondria, a major site of reactive oxygen species (ROS) production, the pro-

cesses involving oxygen could generate highly reactive oxyradicals within the cardiac

cells and this when uncontrolled can cause an imbalance in the redox equilibrium

towards oxidant that can have far-reaching consequences on the basic metabolic pro-

cesses. This can mount oxidative stress (OS) driving the processes related to oxidative

damage eventually leading to cardiac dysfunction and heart failure [ 55 , 56 ]. Loss of

redox control within the cell and the resultant OS can disrupt numerous physiological

functions including but not limited to gene expression, cell survival/apoptosis, cardio-

myocyte differentiation, impaired functions of enzymes, proteins and transcription

factors, excitation-contraction coupling of heart, regulation of blood flow etc., and

perturb cellular integrity and organ homeostasis [ 55 – 60 ]. These effects vary in mag-

nitude depending on the cellular context and the extent of redox disturbance. It has

long been recognized that an acute toxic and chronic “disruption of oxygen metabo-

lism and redox regulation” is a crucial determinant to major cardiovascular problems,

if left untreated, the disease can advance to chronic phase and cause multi-organ fail-

ure eventually proving fatal [ 61 ]. In short, the obligatory redox mechanisms crucial

for basic life-sustaining processes can turn into devastating life-events.

Recent epidemiological studies indicate an increased incidence of CVD among

the aged population (>65  years) in the United States in the past years [ 5 , 62 – 64 ].

Strikingly, the recent health status of the United States compiled by Centers for

Disease Control and Prevention’s (CDC) National Center for Health Statistics

(NCHS) reports that mortality due to cardiac diseases occupy 5th, 3rd, 2nd and 1st

spot in the age group <25, 25–44, 45–64 and over 65  years of age, respectively

(CDC-National Center for Health Statistics, 2015). This provides a compelling point

that the diseases of the heart has a strong correlation with age and is the number one

cause of death in the elderly population. Relevant to these facts, an uncontrolled OS

has been associated strongly with the etiology of stroke, coronary heart disease, isch-

emia/reperfusion injury, atherosclerosis, and hypertension [ 57 , 65 – 67 ]. Further, due

to inherent nature of the heart cells to undergo limited mitosis coupled with the attri-

tion of biosynthetic processes and increased oxidative burden in aging, the ability of

the heart to sustain its structure-function relationships and keeping up the cardiac

performance can be remarkably affected. Thus, age-associated OS has been regarded

as an independent factor to profoundly impact CVD and heart failure [ 55 , 68 , 69 ].

M. Narasimhan and N.-S. Rajasekaran