Page 304 - Read Online

Page 2 of 19 Cervantes-Gracia et al. Vessel Plus 2020;4:27 I http://dx.doi.org/10.20517/2574-1209.2020.22

INTRODUCTION
Inflammation is an immune system response to pathogenic insults and is physiologically important to
protect the organism from injury. Inflammatory responses are triggered by harmful stimuli and lead to
[1]
a removal of invading pathogens and initiation of the healing process . Reactive oxygen species (ROS)
modulate the inflammatory processes [2-5] . ROS include chemically heterogeneous free radicals (e.g.,
[6]
superoxide) and non-radicals (e.g., hydrogen peroxide) vital for cell development, survival and signaling .
[7,8]
Redox signaling occurs through posttranslational oxidation of proteins (e.g., cysteine residues) .
Moreover, there is also a known cross-talk between ROS and neutrophil inflammation clearance and
[5,9]
pro-inflammatory markers . Usually, these mechanisms are tightly regulated and when sustained and
aberrant, inflammatory responses and ROS can lead to tissue damage and disease.

Environmental stress can cause oxidative stress, often defined by cell/tissue injury and attendant oxidative
macromolecule damage . Moreover, ROS have been highlighted as a cause of several inflammatory
[10]
diseases like cardiovascular diseases (CVD), type II diabetes and cancer.

Due to its role promoting inflammation and lipid peroxidation, ROS have been tightly linked to
CVD . Thus, both inflammatory elements and ROS are CVD risk factors, described as underlying
[11]
participants in the progression of atherogenesis. In addition, chronic inflammatory diseases, characterized
by an involvement of oxidative stress in their pathogenesis, promote high risk and influence CVD
susceptibility [12,13] . Inflammatory molecules and ROS have been proposed as possible predictors and drug
targets in CVDs, reviewed by Cervantes Gracia, Llanas-Cornejo, & Husi, 2017 [14,15] . Interestingly, target
organ damage, described as the strong association with high blood pressure and functional changes in the
heart, brain, eyes and kidney, is known to have significant implications in CVD onset [16,17] . Furthermore,
CVD is a characteristic hallmark of severe kidney failure. Patients with chronic kidney disease (CKD) have
been well characterized to carry a significantly higher risk of developing and dying from severe CVDs [18-20] .
Therefore, management of chronic kidney disease progression has been proposed as strategy to reduce the
incidence of cardiovascular events . Conversely, the presence of CVDs have also been associated with a
[21]
[22]
higher risk of renal impairment and CKD progression . However, the influence that one disease has over
the other, as well as the underlying molecular mechanisms remain to be elucidated.

To add to this pathology, kidney failure exacerbated by coronary intervention procedures relying on
contrast media (CM), known as contrast induced nephropathy (CIN), constantly increases the incidence
of comorbidities in this group of patients undergoing interventions and its prevention is challenging [23-26] .
Since pre-existing CKD is the most common cause of CIN [27,28] , the interplay among the underlying
mechanisms of CVD and kidney failure are important. Additionally, inflammation and ROS have been
identified as risk factors of CIN and as potential targets for prophylaxis or treatment [29-34] . Hence, the
elucidation of CIN/CVD interplay in this setting would improve understanding of the signaling processes
and progression of the diseases, leading the way to different approaches to either early detection or to
identification of novel drug targets.

CIN PATHOPHYSIOLOGY IN THE CONTEXT OF CVD
According to the WHO, non-communicable diseases (NCD) account for 71% of all deaths world-wide
and CVDs are responsible for most NCD deaths. CVDs were responsible for about 17.8 million deaths
in 2017 [35,36] , and are the primary cause of death globally. Notably, angioplasty is the most common
percutaneous coronary intervention (PCI) method for CVD treatment [37,38] , and diagnostic angiography
and PCI routinely utilize iodinated CM for vascular visualization [39,40] . Although angiograms and PCI can
effectively diagnose and treat CVD patients, this can potentially lead to acute kidney diseases such as CIN
induced by CM [41-46] . CM can be retained by the kidney where they have the potential to cause toxicity,